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Artikel ; Online: Nutritional compensation of the circadian clock is a conserved process influenced by gene expression regulation and mRNA stability.

Kelliher, Christina M / Stevenson, Elizabeth-Lauren / Loros, Jennifer J / Dunlap, Jay C

2023 Band 21, Heft 1, Seite(n) e3001961

Abstract: Compensation is a defining principle of a true circadian clock, where its approximately 24-hour period length is relatively unchanged across environmental conditions. Known compensation effectors directly regulate core clock factors to buffer the ... ...

Abstract	Compensation is a defining principle of a true circadian clock, where its approximately 24-hour period length is relatively unchanged across environmental conditions. Known compensation effectors directly regulate core clock factors to buffer the oscillator's period length from variables in the environment. Temperature Compensation mechanisms have been experimentally addressed across circadian model systems, but much less is known about the related process of Nutritional Compensation, where circadian period length is maintained across physiologically relevant nutrient levels. Using the filamentous fungus Neurospora crassa, we performed a genetic screen under glucose and amino acid starvation conditions to identify new regulators of Nutritional Compensation. Our screen uncovered 16 novel mutants, and together with 4 mutants characterized in prior work, a model emerges where Nutritional Compensation of the fungal clock is achieved at the levels of transcription, chromatin regulation, and mRNA stability. However, eukaryotic circadian Nutritional Compensation is completely unstudied outside of Neurospora. To test for conservation in cultured human cells, we selected top hits from our fungal genetic screen, performed siRNA knockdown experiments of the mammalian orthologs, and characterized the cell lines with respect to compensation. We find that the wild-type mammalian clock is also compensated across a large range of external glucose concentrations, as observed in Neurospora, and that knocking down the mammalian orthologs of the Neurospora compensation-associated genes CPSF6 or SETD2 in human cells also results in nutrient-dependent period length changes. We conclude that, like Temperature Compensation, Nutritional Compensation is a conserved circadian process in fungal and mammalian clocks and that it may share common molecular determinants.
Mesh-Begriff(e)	Humans ; Circadian Clocks/genetics ; Circadian Rhythm/genetics ; Fungal Proteins/metabolism ; Gene Expression Regulation, Fungal ; Glucose/metabolism ; Neurospora crassa/genetics ; Neurospora crassa/metabolism ; RNA Stability/genetics ; Nutrients/metabolism
Chemische Substanzen	Fungal Proteins ; Glucose (IY9XDZ35W2)
Sprache	Englisch
Erscheinungsdatum	2023-01-05
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2126776-5
ISSN	1545-7885 ; 1544-9173
ISSN (online)	1545-7885
ISSN	1544-9173
DOI	10.1371/journal.pbio.3001961
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Alignment of Synchronized Time-Series Data Using the Characterizing Loss of Cell Cycle Synchrony Model for Cross-Experiment Comparisons.

Campione, Sophia A / Kelliher, Christina M / Orlando, David A / Tran, Trung Q / Haase, Steven B

Journal of visualized experiments : JoVE

2023 , Heft 196

Abstract: Investigating the cell cycle often depends on synchronizing cell populations to measure various parameters in a time series as the cells traverse the cell cycle. However, even under similar conditions, replicate experiments display differences in the ... ...

Abstract	Investigating the cell cycle often depends on synchronizing cell populations to measure various parameters in a time series as the cells traverse the cell cycle. However, even under similar conditions, replicate experiments display differences in the time required to recover from synchrony and to traverse the cell cycle, thus preventing direct comparisons at each time point. The problem of comparing dynamic measurements across experiments is exacerbated in mutant populations or in alternative growth conditions that affect the synchrony recovery time and/or the cell-cycle period. We have previously published a parametric mathematical model named Characterizing Loss of Cell Cycle Synchrony (CLOCCS) that monitors how synchronous populations of cells release from synchrony and progress through the cell cycle. The learned parameters from the model can then be used to convert experimental time points from synchronized time-series experiments into a normalized time scale (lifeline points). Rather than representing the elapsed time in minutes from the start of the experiment, the lifeline scale represents the progression from synchrony to cell-cycle entry and then through the phases of the cell cycle. Since lifeline points correspond to the phase of the average cell within the synchronized population, this normalized time scale allows for direct comparisons between experiments, including those with varying periods and recovery times. Furthermore, the model has been used to align cell-cycle experiments between different species (e.g., Saccharomyces cerevisiae and Schizosaccharomyces pombe), thus enabling direct comparison of cell-cycle measurements, which may reveal evolutionary similarities and differences.
Mesh-Begriff(e)	Time Factors ; Cell Division ; Cell Cycle ; Saccharomyces cerevisiae/genetics ; Schizosaccharomyces
Sprache	Englisch
Erscheinungsdatum	2023-06-09
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Video-Audio Media ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/65466
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Connecting virulence pathways to cell-cycle progression in the fungal pathogen Cryptococcus neoformans.

Kelliher, Christina M / Haase, Steven B

Current genetics

2017 Band 63, Heft 5, Seite(n) 803–811

Abstract: Proliferation and host evasion are critical processes to understand at a basic biological level for improving infectious disease treatment options. The human fungal pathogen Cryptococcus neoformans causes fungal meningitis in immunocompromised ... ...

Abstract	Proliferation and host evasion are critical processes to understand at a basic biological level for improving infectious disease treatment options. The human fungal pathogen Cryptococcus neoformans causes fungal meningitis in immunocompromised individuals by proliferating in cerebrospinal fluid. Current antifungal drugs target "virulence factors" for disease, such as components of the cell wall and polysaccharide capsule in C. neoformans. However, mechanistic links between virulence pathways and the cell cycle are not as well studied. Recently, cell-cycle synchronized C. neoformans cells were profiled over time to identify gene expression dynamics (Kelliher et al., PLoS Genet 12(12):e1006453, 2016). Almost 20% of all genes in the C. neoformans genome were periodically activated during the cell cycle in rich media, including 40 genes that have previously been implicated in virulence pathways. Here, we review important findings about cell-cycle-regulated genes in C. neoformans and provide two examples of virulence pathways-chitin synthesis and G-protein coupled receptor signaling-with their putative connections to cell division. We propose that a "comparative functional genomics" approach, leveraging gene expression timing during the cell cycle, orthology to genes in other fungal species, and previous experimental findings, can lead to mechanistic hypotheses connecting the cell cycle to fungal virulence.
Mesh-Begriff(e)	Cell Cycle ; Chitin/biosynthesis ; Cryptococcosis/microbiology ; Cryptococcus neoformans/physiology ; Gene Expression Regulation, Fungal ; Gene Regulatory Networks ; Protein Binding ; Protein Subunits/genetics ; Protein Subunits/metabolism ; Receptors, G-Protein-Coupled/chemistry ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction ; Virulence/genetics ; Virulence Factors/genetics
Chemische Substanzen	Protein Subunits ; Receptors, G-Protein-Coupled ; Virulence Factors ; Chitin (1398-61-4)
Sprache	Englisch
Erscheinungsdatum	2017-10
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Review
ZDB-ID	282876-5
ISSN	1432-0983 ; 0172-8083
ISSN (online)	1432-0983
ISSN	0172-8083
DOI	10.1007/s00294-017-0688-5
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Evaluating the circadian rhythm and response to glucose addition in dispersed growth cultures of Neurospora crassa.

Kelliher, Christina M / Loros, Jennifer J / Dunlap, Jay C

Fungal biology

2019 Band 124, Heft 5, Seite(n) 398–406

Abstract: Work on the filamentous fungus Neurospora crassa has contributed to or pioneered many aspects of research on circadian clock mechanism, a process that is functionally conserved across eukaryotes. Biochemical assays of the fungal circadian clock typically ...

Abstract	Work on the filamentous fungus Neurospora crassa has contributed to or pioneered many aspects of research on circadian clock mechanism, a process that is functionally conserved across eukaryotes. Biochemical assays of the fungal circadian clock typically involve growth in liquid medium where Neurospora forms a spherical ball of submerged mycelium. Here, we revive a method for dispersed growth of Neurospora in batch culture using polyacrylic acid as an additive to the medium. We demonstrate that dispersed growth cultures utilize more carbon than mycelial balls, but nonetheless retain a functional circadian clock. This culturing method is suited for use in circadian experiments where uniform exposure to nutrients and/or increased biomass is required.
Mesh-Begriff(e)	Circadian Rhythm/drug effects ; Culture Techniques ; Glucose/pharmacology ; Neurospora crassa/drug effects ; Neurospora crassa/growth & development
Chemische Substanzen	Glucose (IY9XDZ35W2)
Sprache	Englisch
Erscheinungsdatum	2019-11-20
Erscheinungsland	Netherlands
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2532164-X
ISSN	1878-6162 ; 1878-6146
ISSN (online)	1878-6162
ISSN	1878-6146
DOI	10.1016/j.funbio.2019.11.004
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: The cell-cycle transcriptional network generates and transmits a pulse of transcription once each cell cycle.

Cho, Chun-Yi / Kelliher, Christina M / Haase, Steven B

Cell cycle (Georgetown, Tex.)

2019 Band 18, Heft 4, Seite(n) 363–378

Abstract: Multiple studies have suggested the critical roles of cyclin-dependent kinases (CDKs) as well as a transcription factor (TF) network in generating the robust cell-cycle transcriptional program. However, the precise mechanisms by which these components ... ...

Abstract	Multiple studies have suggested the critical roles of cyclin-dependent kinases (CDKs) as well as a transcription factor (TF) network in generating the robust cell-cycle transcriptional program. However, the precise mechanisms by which these components function together in the gene regulatory network remain unclear. Here we show that the TF network can generate and transmit a "pulse" of transcription independently of CDK oscillations. The premature firing of the transcriptional pulse is prevented by early G1 inhibitors, including transcriptional corepressors and the E3 ubiquitin ligase complex APC
Mesh-Begriff(e)	Biological Clocks/genetics ; CDC2 Protein Kinase/metabolism ; Cdh1 Proteins/metabolism ; Cell Communication/genetics ; Cell Cycle Checkpoints/genetics ; Gene Deletion ; Gene Regulatory Networks ; Repressor Proteins/genetics ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcription, Genetic/genetics ; Ubiquitin-Protein Ligase Complexes/metabolism
Chemische Substanzen	Cdh1 Proteins ; Repressor Proteins ; STB1 protein, S cerevisiae ; Saccharomyces cerevisiae Proteins ; Transcription Factors ; Whi5 protein, S cerevisiae ; Ubiquitin-Protein Ligase Complexes (EC 2.3.2.23) ; CDC2 Protein Kinase (EC 2.7.11.22)
Sprache	Englisch
Erscheinungsdatum	2019-02-05
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2146183-1
ISSN	1551-4005 ; 1538-4101 ; 1554-8627
ISSN (online)	1551-4005
ISSN	1538-4101 ; 1554-8627
DOI	10.1080/15384101.2019.1570655
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Evaluating the circadian rhythm and response to glucose addition in dispersed growth cultures of Neurospora crassa

Kelliher, Christina M / Loros, Jennifer J / Dunlap, Jay C

British Mycological Society Fungal biology. 2020 May, v. 124, no. 5

2020

Abstract	Work on the filamentous fungus Neurospora crassa has contributed to or pioneered many aspects of research on circadian clock mechanism, a process that is functionally conserved across eukaryotes. Biochemical assays of the fungal circadian clock typically involve growth in liquid medium where Neurospora forms a spherical ball of submerged mycelium. Here, we revive a method for dispersed growth of Neurospora in batch culture using polyacrylic acid as an additive to the medium. We demonstrate that dispersed growth cultures utilize more carbon than mycelial balls, but nonetheless retain a functional circadian clock. This culturing method is suited for use in circadian experiments where uniform exposure to nutrients and/or increased biomass is required.
Schlagwörter	Neurospora crassa ; biomass ; carbon ; circadian clocks ; circadian rhythm ; eukaryotic cells ; fungi ; glucose ; liquids ; mycelium ; nutrients ; polyacrylic acid
Sprache	Englisch
Erscheinungsverlauf	2020-05
Umfang	p. 398-406.
Erscheinungsort	Elsevier Ltd
Dokumenttyp	Artikel
ZDB-ID	2532164-X
ISSN	1878-6162 ; 1878-6146
ISSN (online)	1878-6162
ISSN	1878-6146
DOI	10.1016/j.funbio.2019.11.004
Datenquelle	NAL Katalog (AGRICOLA)

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Artikel: Connecting virulence pathways to cell-cycle progression in the fungal pathogen Cryptococcus neoformans

Kelliher, Christina M / Steven B. Haase

Current genetics. 2017 Oct., v. 63, no. 5

2017

Abstract	Proliferation and host evasion are critical processes to understand at a basic biological level for improving infectious disease treatment options. The human fungal pathogen Cryptococcus neoformans causes fungal meningitis in immunocompromised individuals by proliferating in cerebrospinal fluid. Current antifungal drugs target âvirulence factorsâ for disease, such as components of the cell wall and polysaccharide capsule in C. neoformans. However, mechanistic links between virulence pathways and the cell cycle are not as well studied. Recently, cell-cycle synchronized C. neoformans cells were profiled over time to identify gene expression dynamics (Kelliher et al., PLoS Genet 12(12):e1006453, 2016). Almost 20% of all genes in the C. neoformans genome were periodically activated during the cell cycle in rich media, including 40 genes that have previously been implicated in virulence pathways. Here, we review important findings about cell-cycle-regulated genes in C. neoformans and provide two examples of virulence pathwaysâchitin synthesis and G-protein coupled receptor signalingâwith their putative connections to cell division. We propose that a âcomparative functional genomicsâ approach, leveraging gene expression timing during the cell cycle, orthology to genes in other fungal species, and previous experimental findings, can lead to mechanistic hypotheses connecting the cell cycle to fungal virulence.
Schlagwörter	Cryptococcus neoformans ; G-protein coupled receptors ; animal pathogenic fungi ; antifungal agents ; cell division ; cerebrospinal fluid ; gene expression ; genes ; genomics ; immunocompromised population ; infectious diseases ; meningitis ; polysaccharides ; therapeutics ; virulence
Sprache	Englisch
Erscheinungsverlauf	2017-10
Umfang	p. 803-811.
Erscheinungsort	Springer Berlin Heidelberg
Dokumenttyp	Artikel
Anmerkung	Review
ZDB-ID	282876-5
ISSN	1432-0983 ; 0172-8083
ISSN (online)	1432-0983
ISSN	0172-8083
DOI	10.1007/s00294-017-0688-5
Datenquelle	NAL Katalog (AGRICOLA)

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Artikel ; Online: PRD-2 directly regulates

Kelliher, Christina M / Lambreghts, Randy / Xiang, Qijun / Baker, Christopher L / Loros, Jennifer J / Dunlap, Jay C

eLife

2020 Band 9

Abstract: Circadian clocks in fungi and animals are driven by a functionally conserved transcription-translation feedback loop. ... ...

Abstract	Circadian clocks in fungi and animals are driven by a functionally conserved transcription-translation feedback loop. In
Mesh-Begriff(e)	Casein Kinase I/metabolism ; Casein Kinase I/physiology ; Circadian Clocks/physiology ; Fungal Proteins/metabolism ; Fungal Proteins/physiology ; Gene Expression Regulation, Fungal ; Genes, Fungal/genetics ; Genes, Fungal/physiology ; Neurospora crassa/enzymology ; Neurospora crassa/genetics ; Neurospora crassa/physiology
Chemische Substanzen	Fungal Proteins ; Casein Kinase I (EC 2.7.11.1)
Sprache	Englisch
Erscheinungsdatum	2020-12-09
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.64007
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Investigating Conservation of the Cell-Cycle-Regulated Transcriptional Program in the Fungal Pathogen, Cryptococcus neoformans.

Kelliher, Christina M / Leman, Adam R / Sierra, Crystal S / Haase, Steven B

PLoS genetics

2016 Band 12, Heft 12, Seite(n) e1006453

Abstract: The pathogenic yeast Cryptococcus neoformans causes fungal meningitis in immune-compromised patients. Cell proliferation in the budding yeast form is required for C. neoformans to infect human hosts, and virulence factors such as capsule formation and ... ...

Abstract	The pathogenic yeast Cryptococcus neoformans causes fungal meningitis in immune-compromised patients. Cell proliferation in the budding yeast form is required for C. neoformans to infect human hosts, and virulence factors such as capsule formation and melanin production are affected by cell-cycle perturbation. Thus, understanding cell-cycle regulation is critical for a full understanding of virulence factors for disease. Our group and others have demonstrated that a large fraction of genes in Saccharomyces cerevisiae is expressed periodically during the cell cycle, and that proper regulation of this transcriptional program is important for proper cell division. Despite the evolutionary divergence of the two budding yeasts, we found that a similar percentage of all genes (~20%) is periodically expressed during the cell cycle in both yeasts. However, the temporal ordering of periodic expression has diverged for some orthologous cell-cycle genes, especially those related to bud emergence and bud growth. Genes regulating DNA replication and mitosis exhibited a conserved ordering in both yeasts, suggesting that essential cell-cycle processes are conserved in periodicity and in timing of expression (i.e. duplication before division). In S. cerevisiae cells, we have proposed that an interconnected network of periodic transcription factors (TFs) controls the bulk of the cell-cycle transcriptional program. We found that temporal ordering of orthologous network TFs was not always maintained; however, the TF network topology at cell-cycle commitment appears to be conserved in C. neoformans. During the C. neoformans cell cycle, DNA replication genes, mitosis genes, and 40 genes involved in virulence are periodically expressed. Future work toward understanding the gene regulatory network that controls cell-cycle genes is critical for developing novel antifungals to inhibit pathogen proliferation.
Mesh-Begriff(e)	Cell Cycle/genetics ; Cell Proliferation/genetics ; Cryptococcus neoformans/genetics ; Cryptococcus neoformans/growth & development ; Cryptococcus neoformans/pathogenicity ; Evolution, Molecular ; Fungal Proteins/biosynthesis ; Fungal Proteins/genetics ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Fungal ; Gene Regulatory Networks/genetics ; Genetic Variation ; Humans ; Mitosis/genetics ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/growth & development ; Transcription, Genetic
Chemische Substanzen	Fungal Proteins
Sprache	Englisch
Erscheinungsdatum	2016-12
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	2186725-2
ISSN	1553-7404 ; 1553-7390
ISSN (online)	1553-7404
ISSN	1553-7390
DOI	10.1371/journal.pgen.1006453
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: The parasite intraerythrocytic cycle and human circadian cycle are coupled during malaria infection.

Motta, Francis C / McGoff, Kevin / Moseley, Robert C / Cho, Chun-Yi / Kelliher, Christina M / Smith, Lauren M / Ortiz, Michael S / Leman, Adam R / Campione, Sophia A / Devos, Nicolas / Chaorattanakawee, Suwanna / Uthaimongkol, Nichaphat / Kuntawunginn, Worachet / Thongpiam, Chadin / Thamnurak, Chatchadaporn / Arsanok, Montri / Wojnarski, Mariusz / Vanchayangkul, Pattaraporn / Boonyalai, Nonlawat /

Smith, Philip L / Spring, Michele D / Jongsakul, Krisada / Chuang, Ilin / Harer, John / Haase, Steven B

Proceedings of the National Academy of Sciences of the United States of America

2023 Band 120, Heft 24, Seite(n) e2216522120

Abstract: During infections with the malaria ... ...

Abstract	During infections with the malaria parasites
Mesh-Begriff(e)	Humans ; Mice ; Animals ; Parasites ; Host-Parasite Interactions ; Malaria/parasitology ; Plasmodium/genetics ; Malaria, Vivax
Sprache	Englisch
Erscheinungsdatum	2023-06-06
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2216522120
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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