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Article ; Online: Pandemic COVID-19: Current status and challenges of antiviral therapies.

Chan, Winglam / He, Betsy / Wang, Xiong / He, Ming-Liang

2020 Volume 7, Issue 4, Page(s) 502–519

Abstract: The pandemic COVID-19, caused by a new coronavirus SARS-CoV-2 infection, has infected over 12 million individuals and caused more than 55,200 death worldwide. Currently, there is no specific drug to treating this disease. Here we summarized the ... ...

Abstract	The pandemic COVID-19, caused by a new coronavirus SARS-CoV-2 infection, has infected over 12 million individuals and caused more than 55,200 death worldwide. Currently, there is no specific drug to treating this disease. Here we summarized the mechanisms of antiviral therapies and the clinic findings from different countries. Antiviral chemotherapies have been conducted by in multiple cohorts in different counties. Although FDA has fast approved remdesivir for treating COVID-19, it only speeds up recovery from COVID-19 with mildly reduced mortality. The chloroquine was suggested a potential drug against SARS-CoV-2 infection due to its
Keywords	covid19
Language	English
Publishing date	2020-07-07
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2821806-1
ISSN	2352-3042 ; 2352-3042
ISSN (online)	2352-3042
ISSN	2352-3042
DOI	10.1016/j.gendis.2020.07.001
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Pandemic COVID-19

Chan, Winglam / He, Betsy / Wang, Xiong / He, Ming-Liang

Genes & Diseases ; ISSN 2352-3042

Current status and challenges of antiviral therapies

2020

Keywords	covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
DOI	10.1016/j.gendis.2020.07.001
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Pandemic COVID-19

Winglam Chan / Betsy He / Xiong Wang / Ming-Liang He

Genes and Diseases, Vol 7, Iss 4, Pp 502-

Current status and challenges of antiviral therapies

2020 Volume 519

Abstract	The pandemic COVID-19, caused by a new coronavirus SARS-CoV-2 infection, has infected over 12 million individuals and caused more than 55,200 death worldwide. Currently, there is no specific drug to treating this disease. Here we summarized the mechanisms of antiviral therapies and the clinic findings from different countries. Antiviral chemotherapies have been conducted by in multiple cohorts in different counties. Although FDA has fast approved remdesivir for treating COVID-19, it only speeds up recovery from COVID-19 with mildly reduced mortality. The chloroquine was suggested a potential drug against SARS-CoV-2 infection due to its in vitro antiviral effects, it is imperative high-quality data from worldwide clinical trials are necessitated for an approved therapy. In terms of hydroxychloroquine (HCQ) therapy, although WHO has stopped all the clinic trials due to its strong side-effects in COVID patients, large scale clinical trials with a long-term outcome follow-up may warrant HCQ and azithromycin combination in combating the virus. Convalescent plasma (CP) therapy suggested its safety use in SARS-CoV-2 infection; but both CP immunotherapy and NK cellular therapy must be manufactured and utilized according to scrupulous ethical and controlled conditions to guarantee a possible role of these products of human origin. Further research should be conducted to define the exact mechanism of SARS-CoV-2 pathogenesis, suitable animal models or ex vivo human lung tissues aid in studying replication, transmission and spread of the novel viruses, thereby facilitating highly effective therapies.
Keywords	Chloroquine ; Convalescent plasma therapy ; COVID-19 ; Hydroxychloroquine ; Ivermectin ; Natural killer cell therapy ; Medicine (General) ; R5-920 ; Genetics ; QH426-470
Subject code	610
Language	English
Publishing date	2020-12-01T00:00:00Z
Publisher	KeAi Communications Co., Ltd.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Pandemic COVID-19: current status and challenges of antiviral therapies

Chan, Winglam / He, Betsy / Wang, Xiong / He, Ming-Liang

Abstract: The pandemic COVID-19, caused by a new coronavirus SARS-CoV-2 infection, has infected over 6 million individuals and caused more than 364,000 death worldwide. Currently, there is no specific drug to treating this disease. Here we summarized the ... ...

Abstract	The pandemic COVID-19, caused by a new coronavirus SARS-CoV-2 infection, has infected over 6 million individuals and caused more than 364,000 death worldwide. Currently, there is no specific drug to treating this disease. Here we summarized the mechanisms of antiviral therapies and the clinic findings from different countries. Antiviral chemotherapies have been conducted by in multiple cohorts in different counties. Although FDA has fast approved remdesivir for treating COVID-19, it only speeds up recovery from COVID-19 with mildly reduced mortality. The chloroquine was suggested a potential drug against SARS-CoV-2 infection due to its in vitro antiviral effects, it is imperative high-quality data from worldwide clinical trials are necessitated for an approved therapy. In terms of hydroxychloroquine (HCQ) therapy, although WHO has stopped all the clinic trials due to its strong side-effects in COVID patients, large scale clinical trials with a long-term outcome follow-up may warrant HCQ and azithromycin combination in combating the virus. Convalescent plasma (CP) therapy suggested its safety use in SARS-CoV-2 infection; but both CP immunotherapy and NK cellular therapy must be manufactured and utilized according to scrupulous ethical and controlled conditions to guarantee a possible role of these products of human origin. Further research should be conducted to define the exact mechanism of SARS-CoV-2 pathogenesis, suitable animal models or ex vivo human lung tissues aid in studying replication, transmission and spread of the novel viruses, thereby facilitating highly effective therapies.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #635583
Database	COVID19

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Article ; Online: Fluorescently Modified NDM-1: A Versatile Drug Sensor for Rapid

Chung, Sai-Fung / Tam, Suet-Ying / Wong, Wai-Ting / So, Pui-Kin / Cheong, Wing-Lam / Mak, Chun-Wing / Lee, Leo Man-Yuen / Chan, Pak-Ho / Wong, Kwok-Yin / Leung, Yun-Chung

ACS omega

2024 Volume 9, Issue 8, Page(s) 9161–9169

Abstract: We successfully developed a fluorescent drug sensor from clinically relevant New Delhi metallo-β-lactamase-1 (NDM-1). The F70 residue was chosen to be replaced with a cysteine for conjugation with thiol-reactive fluorescein-5-maleimide to form ... ...

Abstract	We successfully developed a fluorescent drug sensor from clinically relevant New Delhi metallo-β-lactamase-1 (NDM-1). The F70 residue was chosen to be replaced with a cysteine for conjugation with thiol-reactive fluorescein-5-maleimide to form fluorescent F70Cf, where "f" refers to fluorescein-5-maleimide. Our proteolytic studies of unlabeled F70C and labeled F70Cf monitored by electrospray ionization-mass spectrometry (ESI-MS) revealed that fluorescein-5-maleimide was specifically linked to C70 in 1:1 mole ratio (F70C:fluorophore). Our drug sensor (F70Cf) can detect the β-lactam antibiotics cefotaxime and cephalothin by giving stronger fluorescence in the initial binding phase and then declining fluorescence signals as a result of the hydrolysis of the antibiotics into acid products. F70Cf can also detect non-β-lactam inhibitors (e.g., l-captopril, d-captopril, dl-thiorphan, and thanatin). In all cases, F70Cf exhibits stronger fluorescence due to inhibitor binding and subsequently sustained fluorescence signals in a later stage. Native ESI-MS results show that F70Cf can bind to all four inhibitors. Moreover, our drug sensor is compatible with a high-throughput microplate reader and has the capability to perform
Language	English
Publishing date	2024-02-13
Publishing country	United States
Document type	Journal Article
ISSN	2470-1343
ISSN (online)	2470-1343
DOI	10.1021/acsomega.3c08117
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Article ; Online: Hydrophobic substituents on isatin derivatives enhance their inhibition against bacterial peptidoglycan glycosyltransferase activity.

Wang, Yong / Cheong, Wing-Lam / Liang, Zhiguang / So, Lok-Yan / Chan, Kin-Fai / So, Pui-Kin / Chen, Yu Wai / Wong, Wing-Leung / Wong, Kwok-Yin

Bioorganic chemistry

2020 Volume 97, Page(s) 103710

Abstract: Moenomycin A, the well-known natural product inhibitor of peptidoglycan glycosyltransferase (PGT), is a large amphiphilic molecule of molecular mass of 1583 g/mol and its bioavailablity as a drug is relatively poor. In searching for small-molecule ... ...

Abstract	Moenomycin A, the well-known natural product inhibitor of peptidoglycan glycosyltransferase (PGT), is a large amphiphilic molecule of molecular mass of 1583 g/mol and its bioavailablity as a drug is relatively poor. In searching for small-molecule ligands with high inhibition ability targeting the enzyme, we found that the addition of hydrophobic groups to an isatin-based inhibitor of bacterial PGT significantly improves its inhibition against the enzyme, as well as its antibacterial activity. The improvement in enzymatic inhibition can be attributed to a better binding of the small molecule inhibitor to the hydrophobic region of the membrane-bound bacterial cell wall synthesis enzyme and the plasma membrane. In the present study, a total of 20 new amphiphilic compounds were systematically designed and the relationship between molecular hydrophobicity and the antibacterial activity by targeting at PGT was demonstrated. The in vitro lipid II transglycosylation inhibitory effects (IC
MeSH term(s)	Anti-Bacterial Agents/chemistry ; Anti-Bacterial Agents/pharmacology ; Bacteria/drug effects ; Bacteria/enzymology ; Bacterial Infections/drug therapy ; Bacterial Infections/microbiology ; Cell Line ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/pharmacology ; Escherichia coli/drug effects ; Escherichia coli/enzymology ; Humans ; Hydrophobic and Hydrophilic Interactions ; Isatin/analogs & derivatives ; Isatin/pharmacology ; Models, Molecular ; Peptidoglycan Glycosyltransferase/antagonists & inhibitors ; Peptidoglycan Glycosyltransferase/metabolism
Chemical Substances	Anti-Bacterial Agents ; Enzyme Inhibitors ; Isatin (82X95S7M06) ; Peptidoglycan Glycosyltransferase (EC 2.4.1.129)
Language	English
Publishing date	2020-02-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120080-x
ISSN	1090-2120 ; 0045-2068
ISSN (online)	1090-2120
ISSN	0045-2068
DOI	10.1016/j.bioorg.2020.103710
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Zs.A 4207: Show issues

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bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: The impact of positron emission tomography on primary tumour delineation and dosimetric outcome in intensity modulated radiotherapy of early T-stage nasopharyngeal carcinoma.

Wu, Vincent W C / Leung, Wan-Shun / Wong, Kwun-Lam / Chan, Ying-Kit / Law, Wing-Lam / Leung, Wing-Kwan / Yu, Yat-Long

Radiation oncology (London, England)

2016 Volume 11, Issue 1, Page(s) 109

Abstract: Background: In intensity modulated radiotherapy (IMRT) of nasopharyngeal carcinoma (NPC), accurate delineation of the gross tumour volume (GTV) is important. Image registration of CT and MRI has been routinely used in treatment planning. With recent ... ...

Abstract	Background: In intensity modulated radiotherapy (IMRT) of nasopharyngeal carcinoma (NPC), accurate delineation of the gross tumour volume (GTV) is important. Image registration of CT and MRI has been routinely used in treatment planning. With recent development of positron emission tomography (PET), the aims of this study were to evaluate the impact of PET on GTV delineation and dosimetric outcome in IMRT of early stage NPC patients. Methods: Twenty NPC patients with T1 or T2 disease treated by IMRT were recruited. For each patient, 2 sets of NP GTVs were delineated separately, in which one set was performed using CT and MRI registration only (GTVCM), while the other set was carried out using PET, CT and MRI information (GTVCMP). A 9-field IMRT plan was computed based on the target volumes generated from CT and MRI (PTVCM). To assess the geometric difference between the GTVCM and GTVCMP, GTV volumes and DICE similarity coefficient (DSC), which measured the geometrical similarity between the two GTVs, were recorded. To evaluate the dosimetric impact, the Dmax, Dmin, Dmean and D95 of PTVs were obtained from their dose volume histograms generated by the treatment planning system. Results: The overall mean volume of GTVCMP was greater than GTVCM by 4.4 %, in which GTVCMP was slightly greater in the T1 group but lower in the T2 group. The mean DSC of the whole group was 0.79 ± 0.05. Similar mean DSC values were also obtained from the T1 and T2 groups separately. The dosimetric parameters of PTVCM fulfilled the planning requirements. When applying this plan to the PTVCMP, the average Dmin (56.9 Gy) and D95 (68.6 Gy) of PTVCMP failed to meet the dose requirements and demonstrated significant differences from the PTVCM (p = 0.001 and 0.016 respectively), whereas the doses to GTVCMP did not show significant difference with the GTVCM. Conclusion: In IMRT of early stage NPC, PET was an important imaging modality in radiotherapy planning so as to avoid underdosing the PTV, although its effect on GTV delineation was not significant. It was recommended that PET images should be included in the treatment planning of NPC patients.
MeSH term(s)	Carcinoma ; Humans ; Magnetic Resonance Imaging ; Multimodal Imaging/methods ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms/diagnostic imaging ; Nasopharyngeal Neoplasms/radiotherapy ; Positron-Emission Tomography ; Radiotherapy Planning, Computer-Assisted/methods ; Radiotherapy, Intensity-Modulated/methods ; Tomography, X-Ray Computed
Language	English
Publishing date	2016-08-24
Publishing country	England
Document type	Journal Article
ISSN	1748-717X
ISSN (online)	1748-717X
DOI	10.1186/s13014-016-0685-8
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Article ; Online: Fluorescent TEM-1 β-lactamase with wild-type activity as a rapid drug sensor for in vitro drug screening

Wing‑Lam Cheong / Ming‑San Tsang / Pui‑Kin So / Wai‑Hong Chung / Yun‑Chung Leung / Pak‑Ho Chan

Bioscience Reports, Vol 34, Iss 5, p e

2014 Volume 00136

Abstract: We report the development of a novel fluorescent drug sensor from the bacterial drug target TEM-1 β-lactamase through the combined strategy of Val216→Cys216 mutation and fluorophore labelling for in vitro drug screening. The Val216 residue in TEM-1 is ... ...

Abstract	We report the development of a novel fluorescent drug sensor from the bacterial drug target TEM-1 β-lactamase through the combined strategy of Val216→Cys216 mutation and fluorophore labelling for in vitro drug screening. The Val216 residue in TEM-1 is replaced with a cysteine residue, and the environment-sensitive fluorophore fluorescein-5-maleimide is specifically attached to the Cys216 residue in the V216C mutant for sensing drug binding at the active site. The labelled V216C mutant has wild-type catalytic activity and gives stronger fluorescence when β-lactam antibiotics bind to the active site. The labelled V216C mutant can differentiate between potent and impotent β-lactam antibiotics and can distinguish active-site binders from non-binders (including aggregates formed by small molecules in aqueous solution) by giving characteristic time-course fluorescence profiles. Mass spectrometric, molecular modelling and trypsin digestion results indicate that drug binding at the active site is likely to cause the fluorescein label to stay away from the active site and experience weaker fluorescence quenching by the residues around the active site, thus making the labelled V216C mutant to give stronger fluorescence in the drug-bound state. Given the ancestor's role of TEM-1 in the TEM family, the fluorescent TEM-1 drug sensor represents a good model to demonstrate the general combined strategy of Val216→Cys216 mutation and fluorophore labelling for fabricating tailor-made fluorescent drug sensors from other clinically significant TEM-type β-lactamase variants for in vitro drug screening.
Keywords	antibiotics ; bacteria ; β-lactamase ; drug screening ; inhibitors ; sensor ; Biology (General) ; QH301-705.5 ; Science ; Q
Language	English
Publishing date	2014-09-01T00:00:00Z
Publisher	Portland Press Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Fluorescent TEM-1 β-lactamase with wild-type activity as a rapid drug sensor for in vitro drug screening.

Cheong, Wing-Lam / Tsang, Ming-San / So, Pui-Kin / Chung, Wai-Hong / Leung, Yun-Chung / Chan, Pak-Ho

Bioscience reports

2014 Volume 34, Issue 5

Abstract	We report the development of a novel fluorescent drug sensor from the bacterial drug target TEM-1 β-lactamase through the combined strategy of Val216→Cys216 mutation and fluorophore labelling for in vitro drug screening. The Val216 residue in TEM-1 is replaced with a cysteine residue, and the environment-sensitive fluorophore fluorescein-5-maleimide is specifically attached to the Cys216 residue in the V216C mutant for sensing drug binding at the active site. The labelled V216C mutant has wild-type catalytic activity and gives stronger fluorescence when β-lactam antibiotics bind to the active site. The labelled V216C mutant can differentiate between potent and impotent β-lactam antibiotics and can distinguish active-site binders from non-binders (including aggregates formed by small molecules in aqueous solution) by giving characteristic time-course fluorescence profiles. Mass spectrometric, molecular modelling and trypsin digestion results indicate that drug binding at the active site is likely to cause the fluorescein label to stay away from the active site and experience weaker fluorescence quenching by the residues around the active site, thus making the labelled V216C mutant to give stronger fluorescence in the drug-bound state. Given the ancestor's role of TEM-1 in the TEM family, the fluorescent TEM-1 drug sensor represents a good model to demonstrate the general combined strategy of Val216→Cys216 mutation and fluorophore labelling for fabricating tailor-made fluorescent drug sensors from other clinically significant TEM-type β-lactamase variants for in vitro drug screening.
MeSH term(s)	Amino Acid Substitution ; Biosensing Techniques ; Catalytic Domain ; Drug Evaluation, Preclinical/methods ; Escherichia coli/enzymology ; Escherichia coli Proteins/chemistry ; Escherichia coli Proteins/genetics ; Mutation, Missense ; beta-Lactamases/chemistry ; beta-Lactamases/genetics ; beta-Lactams/analysis ; beta-Lactams/chemistry
Chemical Substances	Escherichia coli Proteins ; beta-Lactams ; beta-Lactamases (EC 3.5.2.6) ; beta-lactamase TEM-1 (EC 3.5.2.6)
Language	English
Publishing date	2014-09-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	764946-0
ISSN	1573-4935 ; 0144-8463
ISSN (online)	1573-4935
ISSN	0144-8463
DOI	10.1042/BSR20140057
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Zs.A 1676: Show issues

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Article ; Online: Gastroprotective therapy does not improve outcomes of patients with Helicobacter pylori-negative idiopathic bleeding ulcers.

Wong, Grace Lai-Hung / Au, Kim Wing-Lam / Lo, Angeline Oi-Shan / Tse, Yee-Kit / Ching, Jessica Yuet-Ling / To, Ka-Fai / Chan, Francis Ka-Leung

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association

2012 Volume 10, Issue 10, Page(s) 1124–1129

Abstract: Background & aims: We performed a prospective cohort study to investigate the effects of gastroprotective agents (such as proton pump inhibitors or histamine-2 receptor antagonists) on long-term clinical outcomes of patients with Helicobacter pylori- ... ...

Abstract	Background & aims: We performed a prospective cohort study to investigate the effects of gastroprotective agents (such as proton pump inhibitors or histamine-2 receptor antagonists) on long-term clinical outcomes of patients with Helicobacter pylori-negative idiopathic bleeding ulcers. Methods: Patients with H pylori-negative idiopathic bleeding ulcers were recruited from a single center from April 2002 to March 2009 (n = 663). Age- and sex-matched patients with H pylori-positive bleeding ulcers were used as controls (n = 633). After ulcers had healed, 566 patients in the H pylori-negative idiopathic ulcer cohort received gastroprotective agents at clinicians' discretion, whereas controls received no gastroprotective agent after H pylori eradication therapy. Patients were followed until September 2011 for end points that included recurrent ulcer bleeding and all-cause mortality. Results: During the exposed period of 534 person-years, the incidence rates of recurrent ulcer bleeding and death were 3.8 (95% confidence interval [CI], 2.6-5.4) and 21.8 (95% CI, 18.8-25.3) per 100 person-years among the patients given gastroprotective agents, compared with incidence rates of 2.4 (95% CI, 1.6-3.5; P = .08) and 13.8 (95% CI, 11.9-16.0; P < .001) per 100 person-years, respectively, during the unexposed period of 1588 person-years. Use of gastroprotective agents was not associated with mortality, after adjusting for confounders (hazard ratio, 1.1; 95% CI, 0.6-1.7). Incident rates of recurrent ulcer bleeding and death were significantly higher in patients with H pylori-negative idiopathic ulcers (2.9 and 17.0 per 100 person-years, respectively) than in controls (1.1 and 5.9 per 100 person-years, respectively; P < .001). Conclusions: Gastroprotective agents do not reduce the risk of recurrent bleeding or mortality for patients with H pylori-negative idiopathic bleeding ulcers.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cohort Studies ; Female ; Gastrointestinal Agents/administration & dosage ; Gastrointestinal Hemorrhage/drug therapy ; Gastrointestinal Hemorrhage/epidemiology ; Gastrointestinal Hemorrhage/mortality ; Humans ; Incidence ; Male ; Middle Aged ; Prospective Studies ; Recurrence ; Treatment Outcome ; Ulcer/complications ; Ulcer/drug therapy ; Ulcer/epidemiology ; Ulcer/mortality ; Young Adult
Chemical Substances	Gastrointestinal Agents
Language	English
Publishing date	2012-10
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2119789-1
ISSN	1542-7714 ; 1542-3565
ISSN (online)	1542-7714
ISSN	1542-3565
DOI	10.1016/j.cgh.2012.06.012
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Zs.A 5836: Show issues

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