全文获取类型
收费全文 | 73篇 |
免费 | 13篇 |
专业分类
86篇 |
出版年
2022年 | 2篇 |
2021年 | 4篇 |
2019年 | 1篇 |
2018年 | 2篇 |
2017年 | 2篇 |
2016年 | 3篇 |
2015年 | 6篇 |
2014年 | 1篇 |
2013年 | 10篇 |
2012年 | 6篇 |
2011年 | 4篇 |
2010年 | 1篇 |
2009年 | 2篇 |
2008年 | 1篇 |
2007年 | 2篇 |
2006年 | 2篇 |
2005年 | 6篇 |
2004年 | 3篇 |
2003年 | 1篇 |
2002年 | 1篇 |
2001年 | 2篇 |
1999年 | 3篇 |
1998年 | 2篇 |
1997年 | 4篇 |
1996年 | 4篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1992年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1874年 | 1篇 |
排序方式: 共有86条查询结果,搜索用时 15 毫秒
1.
2.
Douglas E Bassett Jr Munira A Basrai Carla Connelly Katherine M Hyland Katsumi Kitagawa Melanie L Mayer Dwight M Morrow Andrew M Page Vicente A Resto Robert V Skibbens Philip Hieter 《Current opinion in genetics & development》1996,6(6):763-766
The completion of the genome sequence of the budding yeast Saccharomyces cerevisiae marks the dawn of an exciting new era in eukaryotic biology that will bring with it a new understanding of yeast, other model organisms, and human beings. This body of sequence data benefits yeast researchers by obviating the need for piecemeal sequencing of genes, and allows researchers working with other organisms to tap into experimental advantages inherent in the yeast system and learn from functionally characterized yeast gene products which are their proteins of interest. In addition, the yeast post-genome sequence era is serving as a testing ground for powerful new technologies, and proven experimental approaches are being applied for the first time in a comprehensive fashion on a complete eukaryotic gene repertoire. 相似文献
3.
John S. Choy Eileen O'Toole Breanna M. Schuster Matthew J. Crisp Tatiana S. Karpova James G. McNally Mark Winey Melissa K. Gardner Munira A. Basrai 《Molecular biology of the cell》2013,24(17):2753-2763
How subunit dosage contributes to the assembly and function of multimeric complexes is an important question with implications in understanding biochemical, evolutionary, and disease mechanisms. Toward identifying pathways that are susceptible to decreased gene dosage, we performed a genome-wide screen for haploinsufficient (HI) genes that guard against genome instability in Saccharomyces cerevisiae. This led to the identification of all three genes (SPC97, SPC98, and TUB4) encoding the evolutionarily conserved γ-tubulin small complex (γ-TuSC), which nucleates microtubule assembly. We found that hemizygous γ-TuSC mutants exhibit higher rates of chromosome loss and increases in anaphase spindle length and elongation velocities. Fluorescence microscopy, fluorescence recovery after photobleaching, electron tomography, and model convolution simulation of spc98/+ mutants revealed improper regulation of interpolar (iMT) and kinetochore (kMT) microtubules in anaphase. The underlying cause is likely due to reduced levels of Tub4, as overexpression of TUB4 suppressed the spindle and chromosome segregation defects in spc98/+ mutants. We propose that γ-TuSC is crucial for balanced assembly between iMTs and kMTs for spindle organization and accurate chromosome segregation. Taken together, the results show how gene dosage studies provide critical insights into the assembly and function of multisubunit complexes that may not be revealed by using traditional studies with haploid gene deletion or conditional alleles. 相似文献
4.
Kentaro Ohkuni Yoshimitsu Takahashi Alyona Fulp Josh Lawrimore Wei-Chun Au Nagesh Pasupala Reuben Levy-Myers Jack Warren Alexander Strunnikov Richard E. Baker Oliver Kerscher Kerry Bloom Munira A. Basrai 《Molecular biology of the cell》2016,27(9):1500-1510
Centromeric histone H3, CENP-ACse4, is essential for faithful chromosome segregation. Stringent regulation of cellular levels of CENP-ACse4 restricts its localization to centromeres. Mislocalization of CENP-ACse4 is associated with aneuploidy in yeast and flies and tumorigenesis in human cells; thus defining pathways that regulate CENP-A levels is critical for understanding how mislocalization of CENP-A contributes to aneuploidy in human cancers. Previous work in budding yeast shows that ubiquitination of overexpressed Cse4 by Psh1, an E3 ligase, partially contributes to proteolysis of Cse4. Here we provide the first evidence that Cse4 is sumoylated by E3 ligases Siz1 and Siz2 in vivo and in vitro. Ubiquitination of Cse4 by the small ubiquitin-related modifier (SUMO)-targeted ubiquitin ligase (STUbL) Slx5 plays a critical role in proteolysis of Cse4 and prevents mislocalization of Cse4 to euchromatin under normal physiological conditions. Accumulation of sumoylated Cse4 species and increased stability of Cse4 in slx5∆ strains suggest that sumoylation precedes ubiquitin-mediated proteolysis of Cse4. Slx5-mediated Cse4 proteolysis is independent of Psh1, since slx5∆ psh1∆ strains exhibit higher levels of Cse4 stability and mislocalization than either slx5∆ or psh1∆ strains. Our results demonstrate a role for Slx5 in ubiquitin-mediated proteolysis of Cse4 to prevent its mislocalization and maintain genome stability. 相似文献
5.
Recognizing chromosomes in trouble: association of the spindle checkpoint protein Bub3p with altered kinetochores and a unique defective centromere 下载免费PDF全文
Spindle checkpoint proteins monitor the interaction of the spindle apparatus with the kinetochores, halting anaphase even if the microtubule attachment of only a single chromosome is altered. In this study, we show that Bub3p of Saccharomyces cerevisiae, an evolutionarily conserved spindle checkpoint protein, exhibits distinct interactions with an altered or defective kinetochore(s). We show for the first time that green fluorescent protein-tagged S. cerevisiae Bub3p (Bub3-GFP) exhibits not only a diffuse nuclear localization pattern but also forms distinct nuclear foci in unperturbed growing and G(2)/M-arrested cells. As Bub3-GFP foci overlap only a subset of kinetochores, we tested a model in which alterations or defects in kinetochore or spindle integrity lead to the distinct enrichment of Bub3p at these structures. In support of our model, kinetochore-associated Bub3-GFP is enriched upon activation of the spindle checkpoint due to nocodazole-induced spindle disassembly, overexpression of the checkpoint kinase Mps1p, or the presence of a defective centromere (CEN). Most importantly, using a novel approach with the chromatin immunoprecipitation (ChIP) technique and genetically engineered defective CEN [CF/CEN6(Delta31)], we determined that Bub3-GFP can associate with a single defective kinetochore. Our studies represent the first comprehensive molecular analysis of spindle checkpoint protein function in the context of a wild-type or defective kinetochore(s) by use of live-cell imaging and the ChIP technique in S. cerevisiae. 相似文献
6.
7.
Guo Y Au WC Shakoury-Elizeh M Protchenko O Basrai M Prinz WA Philpott CC 《The Journal of biological chemistry》2010,285(50):39564-39573
Arn1 is an integral membrane protein that mediates the uptake of ferrichrome, an important nutritional source of iron, in Saccharomyces cerevisiae. In the absence of ferrichrome, Arn1p is sorted directly from the trans-Golgi network to the vacuolar lumen for degradation. In the presence of low levels of ferrichrome, the siderophore binds to a receptor domain on Arn1, triggering the redistribution of Arn1 to the plasma membrane. When extracellular ferrichrome levels are high, Arn1 cycles between the plasma membrane and intracellular vesicles. To further understand the mechanisms of trafficking of Arn1p, we screened 4580 viable yeast deletion mutants for mislocalization of Arn1-GFP using synthetic genetic array technology. We identified over 100 genes required for trans-Golgi network-to-vacuole trafficking of Arn1-GFP and only two genes, SER1 and SER2, required for the ferrichrome-induced plasma membrane trafficking of Arn1-GFP. SER1 and SER2 encode two enzymes of the major serine biosynthetic pathway, and the Arn1 trafficking defect in the ser1Δ strain was corrected with supplemental serine or glycine. Plasma membrane trafficking of Hxt3, a structurally related glucose transporter, was unaffected by SER1 deletion. Serine is required for the synthesis of multiple cellular components, including purines, sphingolipids, and phospholipids, but of these only phosphatidylserine corrected the Arn1 trafficking defects of the ser1Δ strain. Strains with defects in phospholipid synthesis also exhibited alterations in Arn1p trafficking, indicating that the intracellular trafficking of some transporters is dependent on the phospholipid composition of the cellular membranes. 相似文献
8.
Stirling PC Crisp MJ Basrai MA Tucker CM Dunham MJ Spencer FA Hieter P 《Chromosoma》2012,121(3):263-275
It has been more than two decades since the original chromosome transmission fidelity (Ctf) screen of Saccharomyces cerevisiae was published. Since that time the spectrum of mutations known to cause Ctf and, more generally, chromosome instability (CIN)
has expanded dramatically as a result of systematic screens across yeast mutant arrays. Here we describe a comprehensive summary
of the original Ctf genetic screen and the cloning of the remaining complementation groups as efforts to expand our knowledge
of the CIN gene repertoire and its mutability in a model eukaryote. At the time of the original screen, it was impossible
to predict either the genes and processes that would be overrepresented in a pool of random mutants displaying a Ctf phenotype
or what the entire set of genes potentially mutable to Ctf would be. We show that in a collection of 136 randomly selected
Ctf mutants, >65% of mutants map to 13 genes, 12 of which are involved in sister chromatid cohesion and/or kinetochore function.
Extensive screening of systematic mutant collections has shown that ~350 genes with functions as diverse as RNA processing
and proteasomal activity mutate to cause a Ctf phenotype and at least 692 genes are required for faithful chromosome segregation.
The enrichment of random Ctf alleles in only 13 of ~350 possible Ctf genes suggests that these genes are more easily mutable
to cause genome instability than the others. These observations inform our understanding of recurring CIN mutations in human
cancers where presumably random mutations are responsible for initiating the frequently observed CIN phenotype of tumors. 相似文献
9.
B Utete C Phiri SS Mlambo N Maringapasi N Muboko TB Fregene 《African Journal of Aquatic Science》2018,43(1):1-15
Concentrations of aluminium, cadmium, chromium, cobalt, copper, iron, lead, nickel and zinc were determined in surface water, benthic sediments, and the gills, liver and stomach muscle tissues of Oreochromis niloticus and Clarias gariepinus in peri-urban lakes Chivero and Manyame, Zimbabwe. Five sites were sampled in each lake once per month in November 2015, February, May, August and November 2016. Pollution load index detected no metal contamination, whereas the geo-accumulation index reflected heavy to extreme sediment pollution, with Fe, Cd, Zn, Cr, Ni and Cu present in both lakes. Significant spatial temporal variations were detected for Al, Cr, Cu and Pb across sites within and between the two lakes. High Fe, Al and Cr concentrations in water and sediments in lakes Chivero and Manyame derive from geogenic background sources in addition to anthropogenic loads and intensity. Elevated concentrations of Al, Pb, Cu, Cd, Fe and Zn detected in gills, liver and stomach tissue of catfish corroborate concentrations in water and sediments, and pose the highest ecological and health risk for hydrobionts in lakes Chivero and Manyame. Contiguity of peri-urban lakes exposes them to similar threats, necessitating creative water management strategies, which ensure ecological continuity. 相似文献
10.
Compost and granular activated carbon biofilters operated at a wastewater treatment plant simultaneously removed low concentrations of hydrogen sulfide and volatile organic compounds. Through the use of phospholipid fatty acid analyses, the effects of declining pH caused by sulfide oxidation were established for microbial growth, microorganism stress, and microbial community structure. Microorganisms on both media demonstrated increases in microbial densities, varying degrees of environmental stress, and domination by gram-negative bacteria. However, the declining pH had little effect on compound removal, which was greater than 99% for the hydrogen sulfide and greater than 70% for the oxygenated and aromatic hydrocarbons. The microbial communities adjusted to difficult environmental conditions through acclimation of the species present or by growth of low-pH-tolerant species. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 53: 296-303, 1997. 相似文献