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Article ; Online: Comprehensive Validation of Diagnostic Next-Generation Sequencing Panels for Acute Myeloid Leukemia Patients.

Wagner, Ulrich / Wong, Christine / Camenisch, Ulrike / Zimmermann, Kathrin / Rechsteiner, Markus / Valtcheva, Nadejda / Theocharides, Alexandre / Widmer, Corinne C / Manz, Markus G / Moch, Holger / Wild, Peter J / Balabanov, Stefan

The Journal of molecular diagnostics : JMD

2022 Volume 24, Issue 8, Page(s) 935–954

Abstract: Next-generation sequencing has greatly advanced the molecular diagnostics of malignant hematological diseases and provides useful information for clinical decision making. Studies have shown that certain mutations are associated with prognosis and have a ...

Abstract	Next-generation sequencing has greatly advanced the molecular diagnostics of malignant hematological diseases and provides useful information for clinical decision making. Studies have shown that certain mutations are associated with prognosis and have a direct impact on treatment of affected patients. Therefore, reliable detection of pathogenic variants is critically important. Here, we compared four sequencing panels with different characteristics, from number of genes covered to technical aspects of library preparation and data analysis workflows, to find the panel with the best clinical utility for myeloid neoplasms with a special focus on acute myeloid leukemia. Using the Acrometrix Oncology Hotspot Control DNA and DNA from acute myeloid leukemia patients, panel performance was evaluated in terms of coverage, precision, recall, and reproducibility and different bioinformatics tools that can be used for the evaluation of any next-generation sequencing panel were tested. Taken together, our results support the reliability of the Acrometrix Oncology Hotspot Control to validate and compare sequencing panels for hematological diseases and show which panel-software combination (platform) has the best performance.
MeSH term(s)	High-Throughput Nucleotide Sequencing/methods ; Humans ; Leukemia, Myeloid, Acute/diagnosis ; Leukemia, Myeloid, Acute/genetics ; Mutation ; Myeloproliferative Disorders/genetics ; Reproducibility of Results
Language	English
Publishing date	2022-06-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2000060-1
ISSN	1943-7811 ; 1525-1578
ISSN (online)	1943-7811
ISSN	1525-1578
DOI	10.1016/j.jmoldx.2022.05.003
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Article: Role of DNA repair in the protection against genotoxic stress.

Camenisch, Ulrike / Naegeli, Hanspeter

EXS

2009 Volume 99, Page(s) 111–150

Abstract: The genome of all organisms is constantly attacked by a variety of environmental and endogenous mutagens that cause cell death, apoptosis, senescence, genetic diseases and cancer. To mitigate these deleterious endpoints of genotoxic reactions, living ... ...

Abstract	The genome of all organisms is constantly attacked by a variety of environmental and endogenous mutagens that cause cell death, apoptosis, senescence, genetic diseases and cancer. To mitigate these deleterious endpoints of genotoxic reactions, living organisms have evolved one or more mechanisms for repairing every type of naturally occurring DNA lesion. For example, double-strand breaks are rapidly religated by non-homologous end-joining. Homologous recombination is used for the high-fidelity repair of interstrand cross-links, double-strand breaks and other DNA injuries that disrupt the replication fork. Some genotoxic lesions inflicted by alkylating agents can be repaired by direct reversal of DNA damage. The base excision repair pathway takes advantage of multiple DNA glycosylases to remove modified or incorrect bases. Finally, the nucleotide excision repair machinery provides a versatile strategy to monitor DNA quality and eliminate all forms of helix-distorting DNA lesions, including a wide diversity of carcinogen adducts. The efficiency of DNA repair responses is enhanced by their coupling to transcription and coordination with the cell cycle circuit.
MeSH term(s)	Animals ; DNA Breaks, Double-Stranded ; DNA Damage ; DNA Glycosylases/metabolism ; DNA Repair/physiology ; Humans ; Models, Biological
Chemical Substances	DNA Glycosylases (EC 3.2.2.-)
Language	English
Publishing date	2009-01-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	1023-294X
ISSN	1023-294X
DOI	10.1007/978-3-7643-8336-7_5
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Article ; Online: HPV-Related Multiphenotypic Sinonasal Carcinoma: Four Cases that Expand the Morpho-Molecular Spectrum and Include Occupational Data.

Rupp, Niels J / Camenisch, Ulrike / Seidl, Kati / Rushing, Elisabeth J / Anderegg, Nanina / Broglie, Martina A / Holzmann, David / Morand, Grégoire B

Head and neck pathology

2019 Volume 14, Issue 3, Page(s) 623–629

Abstract: HPV-related multiphenotypic sinonasal carcinoma (HMSC) is a recently described distinct tumor entity of the sinonasal tract associated with high-risk subtypes of human papilloma virus (HPV), predominantly type 33. The biological behavior seems to be less ...

Abstract	HPV-related multiphenotypic sinonasal carcinoma (HMSC) is a recently described distinct tumor entity of the sinonasal tract associated with high-risk subtypes of human papilloma virus (HPV), predominantly type 33. The biological behavior seems to be less aggressive than the often high-grade, highly proliferative morphology implies; however, recurrences are frequent. Most of the cases present as polypoid tumors within the nasal cavity. Microscopic morphology frequently encompasses adenoid cystic-like features or features reminiscent of other salivary gland tumors. Here, we describe four cases of this rare entity, all observed in women. The polypoid tumors were within the nasal cavity, leading to obstruction, facial pain and epistaxis. The morphology was predominantly basaloid, solid and adenoid cystic-like in two of four cases, one with additional glomeruloid features. Another case showed basaloid tumor cells with prominent mature squamous differentiation and extensive keratinization. A single case showed a predominantly solid and reticular growth pattern. All cases were diffusely positive for p16 (100%), expressed SOX10, LEF-1 and partially S-100, and harbored HPV high-risk types 33, 56 (2×) and 82. No recurrences or metastases were detectable after 3-50 months of follow-up. Of note, three of four patients were nurses/nursing assistant. We expand the morphological spectrum by describing a glomeruloid growth pattern and extensive mature keratinization, and add HPV type 82 to the molecular spectrum. The finding of HMSC among predominantly nurses in our cohort warrants further epidemiological studies in larger cohorts.
MeSH term(s)	Aged ; Carcinoma/pathology ; Carcinoma/virology ; Female ; Humans ; Middle Aged ; Nose Neoplasms/pathology ; Nose Neoplasms/virology ; Nurses ; Papillomaviridae ; Papillomavirus Infections/complications
Language	English
Publishing date	2019-09-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2407834-7
ISSN	1936-0568 ; 1936-055X
ISSN (online)	1936-0568
ISSN	1936-055X
DOI	10.1007/s12105-019-01079-1
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Article ; Online: A 72-year old female with multiple supra- and infratentorial dural masses.

Kirschenbaum, Daniel / Woernle, Christoph / Haralambieva, Eugenia / Marques Maggio, Ewerton / Bernays, René / Camenisch, Ulrike / Rushing, Elisabeth J

Brain pathology (Zurich, Switzerland)

2019 Volume 28, Issue 6, Page(s) 1023–1024

MeSH term(s)	Aged ; Diagnosis, Differential ; Dura Mater/pathology ; Emperipolesis ; Erdheim-Chester Disease/diagnosis ; Erdheim-Chester Disease/diagnostic imaging ; Erdheim-Chester Disease/drug therapy ; Female ; Giant Cells/pathology ; Humans ; Lymphoma/diagnosis ; Macrophages/pathology ; Meningioma/diagnosis ; Mutation ; Positron Emission Tomography Computed Tomography ; Protein Kinase Inhibitors/therapeutic use ; Proto-Oncogene Proteins B-raf/antagonists & inhibitors ; Proto-Oncogene Proteins B-raf/genetics ; Treatment Outcome ; Vemurafenib/therapeutic use
Chemical Substances	Protein Kinase Inhibitors ; Vemurafenib (207SMY3FQT) ; BRAF protein, human (EC 2.7.11.1) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1)
Language	English
Publishing date	2019-01-28
Publishing country	Switzerland
Document type	Case Reports ; Journal Article
ZDB-ID	1051484-3
ISSN	1750-3639 ; 1015-6305
ISSN (online)	1750-3639
ISSN	1015-6305
DOI	10.1111/bpa.12666
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Article: XPA gene, its product and biological roles.

Camenisch, Ulrike / Nägeli, Hanspeter

Advances in experimental medicine and biology

2008 Volume 637, Page(s) 28–38

Abstract: The 31 kDa XPA protein is part of the core incision complex of the mammalian nucleotide excision repair (NER) system and interacts with DNA as well as with many other NER subunits. In the absence of XPA, no incision complex can form and no excision of ... ...

Abstract	The 31 kDa XPA protein is part of the core incision complex of the mammalian nucleotide excision repair (NER) system and interacts with DNA as well as with many other NER subunits. In the absence of XPA, no incision complex can form and no excision of damaged DNA damage occurs. A comparative analysis of the DNA-binding properties in the presence of different substrate conformations indicated that XPA protein interacts preferentially with kinked DNA backbones. The DNA-binding domain of XPA protein displays a positively charged deft that is involved in an indirect readout mechanism, presumably by detecting the increased negative potential encountered at sharp DNA bends. We propose that this indirect recognition function contributes to damage verification by probing the susceptibility of the DNA substrate to be kinked during the assembly of NER complexes.
MeSH term(s)	Humans ; Xeroderma Pigmentosum/genetics ; Xeroderma Pigmentosum Group A Protein/physiology
Chemical Substances	XPA protein, human ; Xeroderma Pigmentosum Group A Protein
Language	English
Publishing date	2008-04-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-0-387-09599-8_4
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Article ; Online: Immunohistochemical detection of PAX-FOXO1 fusion proteins in alveolar rhabdomyosarcoma using breakpoint specific monoclonal antibodies.

Azorsa, David O / Bode, Peter K / Wachtel, Marco / Cheuk, Adam Tai Chi / Meltzer, Paul S / Vokuhl, Christian / Camenisch, Ulrike / Khov, Huy Leng / Bode, Beata / Schäfer, Beat W / Khan, Javed

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

2020 Volume 34, Issue 4, Page(s) 748–757

Abstract: Alveolar Rhabdomyosarcoma (ARMS) is an aggressive pediatric cancer with about 80% of cases characterized by either a t(1;13)(p36;q14) or t(2;13)(q35;q14), which results in the formation of the fusion oncogenes PAX7-FOXO1 and PAX3-FOXO1, respectively. ... ...

Abstract	Alveolar Rhabdomyosarcoma (ARMS) is an aggressive pediatric cancer with about 80% of cases characterized by either a t(1;13)(p36;q14) or t(2;13)(q35;q14), which results in the formation of the fusion oncogenes PAX7-FOXO1 and PAX3-FOXO1, respectively. Since patients with fusion-positive ARMS (FP-RMS) have a poor prognosis and are treated with an aggressive therapeutic regimen, correct classification is of clinical importance. Detection of the translocation by different molecular methods is used for diagnostics, including fluorescence in situ hybridization and RT-PCR or NGS based approaches. Since these methods are complex and time consuming, we developed specific monoclonal antibodies (mAbs) directed to the junction region on the PAX3-FOXO1 fusion protein. Two mAbs, PFM.1 and PFM.2, were developed and able to immunoprecipitate in vitro-translated PAX3-FOXO1 and cellular PAX3-FOXO1 from FP-RMS cells. Furthermore, the mAbs recognized a 105 kDa band in PAX3-FOXO1-transfected cells and in FP-RMS cell lines. The mAbs did not recognize proteins in fusion-negative embryonal rhabdomyosarcoma cell lines, nor did they recognize PAX3 or FOXO1 alone when compared to anti-PAX3 and anti-FOXO1 antibodies. We next evaluated the ability of mAb PFM.2 to detect the fusion protein by immunohistochemistry. Both PAX3-FOXO1 and PAX7-FOXO1 were detected in HEK293 cells transfected with the corresponding cDNAs. Subsequently, we stained 26 primary tumor sections and a rhabdomyosarcoma tissue array and detected both fusion proteins with a positive predictive value of 100%, negative predictive value of 98%, specificity of 100% and a sensitivity of 91%. While tumors are stained homogenously in PAX3-FOXO1 cases, the staining pattern is heterogenous with scattered positive cells only in tumors expressing PAX7-FOXO1. No staining was observed in stromal cells, embryonal rhabdomyosarcoma, and fusion-negative rhabdomyosarcoma. These results demonstrate that mAbs specific for the chimeric oncoproteins PAX3-FOXO1 and PAX7-FOXO1 can be used efficiently for simple and fast subclassification of rhabdomyosarcoma in routine diagnostics via immunohistochemical detection.
MeSH term(s)	Adolescent ; Adult ; Animals ; Antibodies, Monoclonal/immunology ; Antibody Specificity ; Biomarkers, Tumor/analysis ; Child ; Child, Preschool ; Female ; HEK293 Cells ; HeLa Cells ; Humans ; Immunohistochemistry ; Infant ; Male ; Mice ; Middle Aged ; NIH 3T3 Cells ; Oncogene Proteins, Fusion/analysis ; Oncogene Proteins, Fusion/immunology ; Paired Box Transcription Factors/analysis ; Paired Box Transcription Factors/immunology ; Predictive Value of Tests ; Reproducibility of Results ; Rhabdomyosarcoma, Alveolar/immunology ; Rhabdomyosarcoma, Alveolar/pathology ; Young Adult
Chemical Substances	Antibodies, Monoclonal ; Biomarkers, Tumor ; Oncogene Proteins, Fusion ; PAX3-FOXO1A fusion protein, human ; PAX7-FOXO1A fusion protein, human ; Paired Box Transcription Factors
Language	English
Publishing date	2020-12-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	645073-8
ISSN	1530-0285 ; 0893-3952
ISSN (online)	1530-0285
ISSN	0893-3952
DOI	10.1038/s41379-020-00719-0
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Zs.A 2450: Show issues

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Book ; Thesis: Diagnostic investigation into the role of Chlamydiae in cases of increased rates of return to oestrus in pigs

Camenisch, Ulrike Gisela

The Veterinary Record ; 6.2004 u.d.T.: Diagnostic investigation into the role of Chlamydiae in cases of increased rates of return to oestrus in pigs (Infektionskrankheiten)

2003

Author's details	vorgelegt von Ulrike Gisela Camenisch
Language	English
Size	S. 593 - 596
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Univ., Diss.--Zürich, 2003
Database	Former special subject collection: coastal and deep sea fishing

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Article ; Online: Fibrin-associated diffuse large B-cell lymphoma in a hemorrhagic cranial arachnoid cyst.

Kirschenbaum, Daniel / Prömmel, Peter / Vasella, Flavio / Haralambieva, Eugenia / Marques Maggio, Ewerton / Reisch, Robert / Beer, Marc / Camenisch, Ulrike / Rushing, Elisabeth J

Acta neuropathologica communications

2017 Volume 5, Issue 1, Page(s) 60

Language	English
Publishing date	2017--07
Publishing country	England
Document type	Letter
ZDB-ID	2715589-4
ISSN	2051-5960 ; 2051-5960
ISSN (online)	2051-5960
ISSN	2051-5960
DOI	10.1186/s40478-017-0463-3
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Article ; Online: Value of immunohistochemistry in the detection of BRAF(V600E) mutations in fine-needle aspiration biopsies of papillary thyroid carcinoma.

Zimmermann, Anne-Katrin / Camenisch, Ulrike / Rechsteiner, Markus P / Bode-Lesniewska, Beata / Rössle, Matthias

Cancer cytopathology

2013 Volume 122, Issue 1, Page(s) 48–58

Abstract: Background: Fine-needle aspiration biopsy (FNAB) is important in the diagnostic establishment of suspicious thyroid nodules. In thyroid neoplasms, mutation of the BRAF gene occurs rather exclusively in papillary thyroid carcinoma (PTC) and results in>98% ...

Abstract	Background: Fine-needle aspiration biopsy (FNAB) is important in the diagnostic establishment of suspicious thyroid nodules. In thyroid neoplasms, mutation of the BRAF gene occurs rather exclusively in papillary thyroid carcinoma (PTC) and results in>98% of the cases in V600E amino acid substitution. In the current study, the authors investigated the diagnostic value of a recently described monoclonal antibody that detects this specific mutation on FNAB specimens from patients with PTC. Methods: BRAF(V600E) status of FNAB cell blocks from 55 patients with PTC was analyzed by immunohistochemistry (IHC) with the new BRAF(V600E) antibody (clone VE1) and by Sanger sequencing (SaS). In discrepant cases, ultra-deep sequencing was also performed. Available corresponding histological specimens were investigated by IHC and, in selected cases, with SaS as well. Results: All cases yielded evaluable IHC staining results of the cell block sections with good interobserver agreement (kappa value, 0.650). Ten tumors (18.2%) demonstrated no staining, 10 tumors (18.2%) demonstrated equivocal staining, 25 tumors (45.4%) demonstrated moderate staining, and 10 tumors (18.2%) demonstrated strong staining. SaS was able to be performed in 48 cases. Nineteen cases demonstrated wild-type BRAF and 29 cases were found to have the BRAF(V600E) mutation. After performing ultra-deep sequencing 1 false-positive and 2 false-negative VE1 IHC cases remained, resulting in a sensitivity of 93.8% and a specificity of 93.8%. Conclusions: BRAF(V600E) mutations in FNAB specimens from patients with PTC can be reliably detected in most cases by IHC with a new mutation-specific antibody. Interpretation of VE1 IHC staining results on cell block slides of PTC can be difficult in some cases.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Biopsy, Fine-Needle/methods ; Carcinoma/genetics ; Carcinoma/pathology ; Carcinoma/surgery ; Carcinoma, Papillary ; Chi-Square Distribution ; Cohort Studies ; Confidence Intervals ; Female ; Gene Expression Regulation, Neoplastic ; High-Throughput Nucleotide Sequencing ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Mutation ; Proto-Oncogene Proteins B-raf/genetics ; Reproducibility of Results ; Retrospective Studies ; Statistics, Nonparametric ; Thyroid Cancer, Papillary ; Thyroid Neoplasms/genetics ; Thyroid Neoplasms/pathology ; Thyroid Neoplasms/surgery
Chemical Substances	BRAF protein, human (EC 2.7.11.1) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1)
Language	English
Publishing date	2013-09-04
Publishing country	United States
Document type	Evaluation Studies ; Journal Article
ZDB-ID	2594979-2
ISSN	1934-6638 ; 1934-662X
ISSN (online)	1934-6638
ISSN	1934-662X
DOI	10.1002/cncy.21352
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Zs.A 6893: Show issues

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Article: Xeroderma pigmentosum complementation group A protein is driven to nucleotide excision repair sites by the electrostatic potential of distorted DNA.

Camenisch, Ulrike / Dip, Ramiro / Vitanescu, Mirela / Naegeli, Hanspeter

DNA repair

2007 Volume 6, Issue 12, Page(s) 1819–1828

Abstract: The presumed DNA-binding cleft of xeroderma pigmentosum group A (XPA) protein, a key regulatory subunit of the eukaryotic nucleotide excision repair complex, displays a distinctive array of 6 positively charged amino acid side chains. Here, the molecular ...

Abstract	The presumed DNA-binding cleft of xeroderma pigmentosum group A (XPA) protein, a key regulatory subunit of the eukaryotic nucleotide excision repair complex, displays a distinctive array of 6 positively charged amino acid side chains. Here, the molecular function of these closely spaced electropositive residues has been tested by systematic site-directed mutagenesis. After the introduction of single amino acid substitutions, the mutants were probed for protein-DNA interactions in electrophoretic mobility shift and photochemical crosslinking assays. This analysis led to the identification of a critical hot-spot for DNA substrate recognition composed of two neighboring lysines at codons 141 and 179 of the human XPA sequence. The replacement of other basic side chains in the DNA interaction domain conferred more moderate defects of substrate binding. When the function of XPA was tested as a fusion product with either mCherry or green-fluorescent protein, a glutamate substitution of one of the positively charged residues at positions 141 and 179 was sufficient to decrease DNA repair activity in human fibroblasts. Thus, the removal of a single cationic side chain abolished DNA-binding activity and significant excision repair defects could be induced by single charge inversions on the XPA surface, indicating that this molecular sensor participates in substrate recognition by monitoring the electrostatic potential of distorted DNA repair sites.
MeSH term(s)	Base Sequence ; Cells, Cultured ; DNA/chemistry ; DNA/metabolism ; DNA Damage ; DNA Repair ; Electrophoretic Mobility Shift Assay ; Humans ; Mutagenesis, Site-Directed ; Static Electricity ; Xeroderma Pigmentosum Group A Protein/genetics ; Xeroderma Pigmentosum Group A Protein/metabolism
Chemical Substances	XPA protein, human ; Xeroderma Pigmentosum Group A Protein ; DNA (9007-49-2)
Language	English
Publishing date	2007-12-01
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2071608-4
ISSN	1568-7856 ; 1568-7864
ISSN (online)	1568-7856
ISSN	1568-7864
DOI	10.1016/j.dnarep.2007.07.011
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