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Article ; Online: Preface. Patenting and related patenting activities.

Mizushina, Yoshiyuki

Recent patents on food, nutrition & agriculture

2014 Volume 6, Issue 1, Page(s) 1

MeSH term(s)	Biotechnology ; Humans ; Patents as Topic
Language	English
Publishing date	2014-10-10
Publishing country	United Arab Emirates
Document type	Introductory Journal Article
ZDB-ID	2486959-4
ISSN	1876-1429 ; 2212-7984
ISSN (online)	1876-1429
ISSN	2212-7984
DOI	10.2174/221279840601141210114453
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Z 7831: Show issues

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Article ; Online: Specific inhibitors of mammalian DNA polymerase species.

Mizushina, Yoshiyuki

Bioscience, biotechnology, and biochemistry

2009 Volume 73, Issue 6, Page(s) 1239–1251

Abstract: In screening of selective inhibitors of eukaryotic DNA polymerases (pols) for 15 years, more than 100 inhibitors have been discovered from natural and chemical sources. Some compounds selectively inhibit the activities of mammalian pols, and in ... ...

Abstract	In screening of selective inhibitors of eukaryotic DNA polymerases (pols) for 15 years, more than 100 inhibitors have been discovered from natural and chemical sources. Some compounds selectively inhibit the activities of mammalian pols, and in particular, dehydroaltenusin and curcumin derivatives, such as monoacetyl-curcumin, were found to be specific inhibitors of pol alpha and pol lambda, respectively. Dehydroaltenusin was isolated from a fungus (Alternaria tennuis), and this compound inhibited cell proliferation of human cancer cell lines by arresting the cells at the S-phase, and was effective in suppressing the growth on nude mice of solid tumors of human cervical cancer cell line HeLa. Curcumin derivatives had anti-12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammatory activity with the same tendency as pol lambda inhibitory activity. These compounds might be useful not only as "molecular probes" for pol research, but also as biomedical and chemotherapeutic drugs for anti-cancer or anti-inflammation.
MeSH term(s)	Animals ; Enzyme Inhibitors/pharmacology ; Humans ; Mammals ; Mice ; Mice, Nude ; Nucleic Acid Synthesis Inhibitors
Chemical Substances	Enzyme Inhibitors ; Nucleic Acid Synthesis Inhibitors
Language	English
Publishing date	2009-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1106450-x
ISSN	1347-6947 ; 0916-8451
ISSN (online)	1347-6947
ISSN	0916-8451
DOI	10.1271/bbb.90121
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Zs.A 4647: Show issues

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Article ; Online: Immunoglobulin G4-related Pleuritis Complicated with Minimal Change Disease.

Mizushina, Yoshiko / Shiihara, Jun / Nomura, Motoko / Ohta, Hiromitsu / Ohyanagi, Fumiyoshi / Morishita, Yoshiyuki / Tsubochi, Hiroyoshi / Tanaka, Akira / Yamaguchi, Yasuhiro

Internal medicine (Tokyo, Japan)

2021 Volume 61, Issue 5, Page(s) 723–728

Abstract: A 70-year-old woman with bilateral pleural effusion and respiratory failure was admitted to our hospital. Nephrotic syndrome due to minimal change disease had been diagnosed four months before admission. Because blood tests and a pleural fluid analysis ... ...

Abstract	A 70-year-old woman with bilateral pleural effusion and respiratory failure was admitted to our hospital. Nephrotic syndrome due to minimal change disease had been diagnosed four months before admission. Because blood tests and a pleural fluid analysis did not reveal the etiology of her condition, we performed a video-assisted thoracoscopic pleural biopsy. No specific thoracoscopic findings were noted. The pathological findings revealed an increase in immunoglobulin G4 (IgG4)-positive cells; IgG4-related pleuritis was diagnosed. Her pleuritis improved with oral corticosteroid therapy. A further investigation was performed on previous kidney samples; however, the etiology of the nephrotic syndrome was not IgG4-related disease but minimal change disease.
MeSH term(s)	Aged ; Female ; Humans ; Immunoglobulin G ; Nephrosis, Lipoid/complications ; Nephrosis, Lipoid/diagnosis ; Nephrosis, Lipoid/pathology ; Pleura/pathology ; Pleural Effusion/etiology ; Pleural Effusion/pathology ; Pleurisy/complications ; Pleurisy/diagnosis
Chemical Substances	Immunoglobulin G
Language	English
Publishing date	2021-09-04
Publishing country	Japan
Document type	Case Reports ; Journal Article
ZDB-ID	32371-8
ISSN	1349-7235 ; 0021-5120 ; 0918-2918
ISSN (online)	1349-7235
ISSN	0021-5120 ; 0918-2918
DOI	10.2169/internalmedicine.7010-20
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Article ; Online: Identification of pheophorbide a as an inhibitor of receptor for advanced glycation end products in Mallotus japonicus.

Matsumoto, Teruki / Matsuno, Michiyo / Ikui, Norihito / Mizushina, Yoshiyuki / Omiya, Yume / Ishibashi, Rikako / Ueda, Taro / Mizukami, Hajime

Journal of natural medicines

2021 Volume 75, Issue 3, Page(s) 675–681

Abstract: Accumulation of advanced glycation end products (AGEs) plays an important role in diabetes, immunoinflammation, and cardiovascular and neurodegenerative diseases. Since AGEs mediate their pathological effects through interaction with receptor for AGEs ( ... ...

Abstract	Accumulation of advanced glycation end products (AGEs) plays an important role in diabetes, immunoinflammation, and cardiovascular and neurodegenerative diseases. Since AGEs mediate their pathological effects through interaction with receptor for AGEs (RAGE), RAGE antagonists would provide a useful therapeutic option for various health disorders. Therefore, in this study, we aimed to identify phytochemicals that would inhibit binding of AGEs to RAGE, which may help develop new drug leads and/or nutraceuticals for AGE-RAGE-related diseases. On screening ethanol extracts obtained from 700 plant materials collected in Myanmar, we found that the ethanol extract from the leaves of Mallotus philippensis inhibited the binding of AGEs to RAGE. We also found that the leaves of M. japonicus, which belongs to the same genera and distributes abundantly in Japan, exhibited the inhibitory activity similar to M. philippensis. Activity-guided fractionation and LC/MS analysis of the ethanol extract of M. japonicus helped identify pheophorbide a (PPBa) as a major component in the active fraction, along with some other pheophorbide derivatives. PPBa exhibited potent inhibitory activity against AGE-RAGE binding, with an IC
MeSH term(s)	Chlorophyll/analogs & derivatives ; Chlorophyll/pharmacology ; Glycation End Products, Advanced/metabolism ; Humans ; Mallotus Plant/chemistry ; Myanmar ; Phytochemicals/pharmacology ; Plant Leaves/chemistry ; Receptor for Advanced Glycation End Products/antagonists & inhibitors
Chemical Substances	Glycation End Products, Advanced ; Phytochemicals ; Receptor for Advanced Glycation End Products ; Chlorophyll (1406-65-1) ; pheophorbide a (IA2WNI2HO2)
Language	English
Publishing date	2021-02-24
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2227540-X
ISSN	1861-0293 ; 1340-3443
ISSN (online)	1861-0293
ISSN	1340-3443
DOI	10.1007/s11418-021-01495-0
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Article ; Online: The Establishment of an Assay to Measure DNA Polymerase-Catalyzed Repair of UVB-Induced DNA Damage in Skin Cells and Screening of DNA Polymerase Enhancers from Medicinal Plants.

Ikeoka, Sawako / Nakahara, Tatsuo / Iwahashi, Hiroyasu / Mizushina, Yoshiyuki

International journal of molecular sciences

2016 Volume 17, Issue 5

Abstract: An in vitro assay method was established to measure the activity of cellular DNA polymerases (Pols) in cultured normal human epidermal keratinocytes (NHEKs) by modifying Pol inhibitor activity. Ultraviolet (UV) irradiation enhanced the activity of Pols, ... ...

Abstract	An in vitro assay method was established to measure the activity of cellular DNA polymerases (Pols) in cultured normal human epidermal keratinocytes (NHEKs) by modifying Pol inhibitor activity. Ultraviolet (UV) irradiation enhanced the activity of Pols, especially DNA repair-related Pols, in the cell extracts of NHEKs. The optimal ultraviolet B (UVB) exposure dose and culture time to upregulate Pols activity was 100 mJ/cm² and 4-h incubation, respectively. We screened eight extracts of medicinal plants for enhancement of UVB-exposed cellular Pols activity using NHEKs, and found that rose myrtle was the strongest Pols enhancer. A Pols' enhancement compound was purified from an 80% ethanol extract of rose myrtle, and piceatannol was isolated by spectroscopic analysis. Induction of Pol activity involved synergy between UVB irradiation and rose myrtle extract and/or piceatannol. Both the extract and piceatannol reduced UVB-induced cyclobutane pyrimidine dimer production, and prevented UVB-induced cytotoxicity. These results indicate that rose myrtle extract and piceatannol, its component, are potential photo-protective candidates for UV-induced skin damage.
MeSH term(s)	Cell Line ; DNA Damage ; DNA Repair/drug effects ; DNA-Directed DNA Polymerase/metabolism ; Humans ; Keratinocytes/drug effects ; Keratinocytes/metabolism ; Keratinocytes/radiation effects ; Plant Extracts/pharmacology ; Plants, Medicinal/chemistry ; Ultraviolet Rays/adverse effects
Chemical Substances	Plant Extracts ; DNA-Directed DNA Polymerase (EC 2.7.7.7)
Language	English
Publishing date	2016-05-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms17050667
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Article: Specific Inhibitors of Mammalian DNA Polymerase Species

MIZUSHINA, Yoshiyuki

Bioscience, biotechnology, and biochemistry. 2009 June 23, v. 73, no. 6

2009

Abstract	In screening of selective inhibitors of eukaryotic DNA polymerases (pols) for 15 years, more than 100 inhibitors have been discovered from natural and chemical sources. Some compounds selectively inhibit the activities of mammalian pols, and in particular, dehydroaltenusin and curcumin derivatives, such as monoacetyl-curcumin, were found to be specific inhibitors of pol α and pol λ, respectively. Dehydroaltenusin was isolated from a fungus (Alternaria tennuis), and this compound inhibited cell proliferation of human cancer cell lines by arresting the cells at the S-phase, and was effective in suppressing the growth on nude mice of solid tumors of human cervical cancer cell line HeLa. Curcumin derivatives had anti-12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammatory activity with the same tendency as pol λ inhibitory activity. These compounds might be useful not only as “molecular probes” for pol research, but also as biomedical and chemotherapeutic drugs for anti-cancer or anti-inflammation.
Keywords	Alternaria ; DNA ; DNA-directed DNA polymerase ; biotechnology ; cell proliferation ; curcumin ; drug therapy ; fungi ; humans ; neoplasm cells ; uterine cervical neoplasms
Language	English
Dates of publication	2009-0623
Size	p. 1239-1251.
Publishing place	Japan Society for Bioscience, Biotechnology, and Agrochemistry
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	1106450-x
ISSN	1347-6947 ; 0916-8451
ISSN (online)	1347-6947
ISSN	0916-8451
DOI	10.1271/bbb.90121
Database	NAL-Catalogue (AGRICOLA)

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Z 1783: Show issues

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Article: Identification of pheophorbide a as an inhibitor of receptor for advanced glycation end products in Mallotus japonicus

Matsumoto, Teruki / Matsuno, Michiyo / Ikui, Norihito / Mizushina, Yoshiyuki / Omiya, Yume / Ishibashi, Rikako / Ueda, Taro / Mizukami, Hajime

Natural medicines. 2021 June, v. 75, no. 3

2021

Abstract	Accumulation of advanced glycation end products (AGEs) plays an important role in diabetes, immunoinflammation, and cardiovascular and neurodegenerative diseases. Since AGEs mediate their pathological effects through interaction with receptor for AGEs (RAGE), RAGE antagonists would provide a useful therapeutic option for various health disorders. Therefore, in this study, we aimed to identify phytochemicals that would inhibit binding of AGEs to RAGE, which may help develop new drug leads and/or nutraceuticals for AGE–RAGE-related diseases. On screening ethanol extracts obtained from 700 plant materials collected in Myanmar, we found that the ethanol extract from the leaves of Mallotus philippensis inhibited the binding of AGEs to RAGE. We also found that the leaves of M. japonicus, which belongs to the same genera and distributes abundantly in Japan, exhibited the inhibitory activity similar to M. philippensis. Activity-guided fractionation and LC/MS analysis of the ethanol extract of M. japonicus helped identify pheophorbide a (PPBa) as a major component in the active fraction, along with some other pheophorbide derivatives. PPBa exhibited potent inhibitory activity against AGE–RAGE binding, with an IC₅₀ value (0.102 μM) comparable to that of dalteparin (0.084 μM). PPBa may be a valuable natural product for use as a therapeutic agent and/or a nutraceutical against various health complications arising from activation of the AGE–RAGE axis.
Keywords	Japan ; Mallotus japonicus ; Mallotus philippensis ; diabetes ; dietary supplements ; ethanol ; fractionation ; phytochemicals ; therapeutics ; Myanmar
Language	English
Dates of publication	2021-06
Size	p. 675-681.
Publishing place	Springer Singapore
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	1201350-x
ISSN	1340-3443
ISSN	1340-3443
DOI	10.1007/s11418-021-01495-0
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: The Establishment of an Assay to Measure DNA Polymerase-Catalyzed Repair of UVB-Induced DNA Damage in Skin Cells and Screening of DNA Polymerase Enhancers from Medicinal Plants

Sawako Ikeoka / Tatsuo Nakahara / Hiroyasu Iwahashi / Yoshiyuki Mizushina

International Journal of Molecular Sciences, Vol 17, Iss 5, p

2016 Volume 667

Abstract	An in vitro assay method was established to measure the activity of cellular DNA polymerases (Pols) in cultured normal human epidermal keratinocytes (NHEKs) by modifying Pol inhibitor activity. Ultraviolet (UV) irradiation enhanced the activity of Pols, especially DNA repair-related Pols, in the cell extracts of NHEKs. The optimal ultraviolet B (UVB) exposure dose and culture time to upregulate Pols activity was 100 mJ/cm2 and 4-h incubation, respectively. We screened eight extracts of medicinal plants for enhancement of UVB-exposed cellular Pols activity using NHEKs, and found that rose myrtle was the strongest Pols enhancer. A Pols’ enhancement compound was purified from an 80% ethanol extract of rose myrtle, and piceatannol was isolated by spectroscopic analysis. Induction of Pol activity involved synergy between UVB irradiation and rose myrtle extract and/or piceatannol. Both the extract and piceatannol reduced UVB-induced cyclobutane pyrimidine dimer production, and prevented UVB-induced cytotoxicity. These results indicate that rose myrtle extract and piceatannol, its component, are potential photo-protective candidates for UV-induced skin damage.
Keywords	DNA polymerases ; enzyme enhancer ; normal human epidermal keratinocytes (NHEK) ; ultraviolet B (UVB) ; rose myrtle ; piceatannol ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	571
Language	English
Publishing date	2016-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Screening of mammalian DNA polymerase and topoisomerase inhibitors from Garcinia mangostana L. and analysis of human cancer cell proliferation and apoptosis.

Onodera, Takefumi / Takenaka, Yukiko / Kozaki, Sachiko / Tanahashi, Takao / Mizushina, Yoshiyuki

International journal of oncology

2016 Volume 48, Issue 3, Page(s) 1145–1154

Abstract: We purified and identified eight xanthones from mangosteen (Garcinia mangostana L.) and investigated whether these compounds inhibited the activities of mammalian DNA polymerases (Pols) and human DNA topoisomerases (Topos). β-Mangostin was the strongest ... ...

Abstract	We purified and identified eight xanthones from mangosteen (Garcinia mangostana L.) and investigated whether these compounds inhibited the activities of mammalian DNA polymerases (Pols) and human DNA topoisomerases (Topos). β-Mangostin was the strongest inhibitor of both mammalian Pols and human Topos among the isolated xanthones, with 50% inhibitory concentration (IC50) values of 6.4-39.6 and 8.5-10 µM, respectively. Thermal transition analysis indicated that β-mangostin did not directly bind to double-stranded DNA, suggesting that this compound directly bound the enzyme protein rather than the DNA substrate. β-Mangostin showed the strongest suppression of human cervical cancer HeLa cell proliferation among the eight compounds tested, with a 50% lethal dose (LD50) of 27.2 µM. This compound halted cell cycle in S phase at 12-h treatment and induced apoptosis. These results suggest that decreased proliferation by β-mangostin may be a result of the inhibition of cellular Pols rather than Topos, and β-mangostin might be an anticancer chemotherapeutic agent.
MeSH term(s)	Animals ; Antineoplastic Agents/chemistry ; Apoptosis ; Caspase 3/metabolism ; Cattle ; Cell Cycle ; Cell Proliferation ; DNA/chemistry ; DNA, Single-Stranded/chemistry ; DNA-Directed DNA Polymerase/metabolism ; Garcinia mangostana/chemistry ; HeLa Cells ; Humans ; Indoles/chemistry ; Inhibitory Concentration 50 ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Nucleic Acid Synthesis Inhibitors/chemistry ; Rats ; Topoisomerase Inhibitors/chemistry ; Xanthones/chemistry
Chemical Substances	Antineoplastic Agents ; DNA, Single-Stranded ; Indoles ; Nucleic Acid Synthesis Inhibitors ; Topoisomerase Inhibitors ; Xanthones ; DAPI (47165-04-8) ; DNA (9007-49-2) ; DNA-Directed DNA Polymerase (EC 2.7.7.7) ; Caspase 3 (EC 3.4.22.-) ; mangostin (U6RIV93RU1)
Language	English
Publishing date	2016-03
Publishing country	Greece
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1154403-x
ISSN	1791-2423 ; 1019-6439
ISSN (online)	1791-2423
ISSN	1019-6439
DOI	10.3892/ijo.2016.3321
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Zs.A 3690: Show issues

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Article ; Online: Inhibition of DNA polymerase λ and associated inflammatory activities of extracts from steamed germinated soybeans.

Mizushina, Yoshiyuki / Kuriyama, Isoko / Yoshida, Hiromi

Food & function

2014 Volume 5, Issue 4, Page(s) 696–704

Abstract: During the screening of selective DNA polymerase (pol) inhibitors from more than 50 plant food materials, we found that the extract from steamed germinated soybeans (Glycine max L.) inhibited human pol λ activity. Among the three processed soybean ... ...

Abstract	During the screening of selective DNA polymerase (pol) inhibitors from more than 50 plant food materials, we found that the extract from steamed germinated soybeans (Glycine max L.) inhibited human pol λ activity. Among the three processed soybean samples tested (boiled soybeans, steamed soybeans, and steamed germinated soybeans), both the hot water extract and organic solvent extract from the steamed germinated soybeans had the strongest pol λ inhibition. We previously isolated two glucosyl compounds, a cerebroside (glucosyl ceramide, AS-1-4, compound ) and a steroidal glycoside (eleutheroside A, compound ), from dried soybean, and these compounds were prevalent in the extracts of the steamed germinated soybeans as pol inhibitors. The hot water and organic solvent extracts of the steamed germinated soybeans and compounds and selectively inhibited the activity of eukaryotic pol λ in vitro but did not influence the activities of other eukaryotic pols, including those from the A-family (pol γ), B-family (pols α, δ, and ε), and Y-family (pols η, ι, and κ), and also showed no effect on the activity of pol β, which is of the same family (X) as pol λ. The tendency for in vitro pol λ inhibition by these extracts and compounds showed a positive correlation with the in vivo suppression of TPA (12-O-tetradecanoylphorbol-13-acetate)-induced inflammation in mouse ear. These results suggest that steamed germinated soybeans, especially the glucosyl compound components, may be useful for their anti-inflammatory properties.
MeSH term(s)	Animals ; DNA Polymerase beta/antagonists & inhibitors ; DNA Polymerase beta/immunology ; Enzyme Inhibitors/administration & dosage ; Female ; Germination ; Humans ; Inflammation/drug therapy ; Inflammation/enzymology ; Inflammation/genetics ; Inflammation/immunology ; Mice ; Mice, Inbred ICR ; Plant Extracts/administration & dosage ; Glycine max/chemistry ; Glycine max/growth & development
Chemical Substances	Enzyme Inhibitors ; Plant Extracts ; DNA polymerase beta2 (EC 2.7.7.-) ; DNA Polymerase beta (EC 2.7.7.7)
Language	English
Publishing date	2014-02-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2612033-1
ISSN	2042-650X ; 2042-6496
ISSN (online)	2042-650X
ISSN	2042-6496
DOI	10.1039/c3fo60650c
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