全文获取类型
收费全文 | 1852篇 |
免费 | 145篇 |
出版年
2023年 | 20篇 |
2022年 | 33篇 |
2021年 | 58篇 |
2020年 | 24篇 |
2019年 | 58篇 |
2018年 | 46篇 |
2017年 | 50篇 |
2016年 | 52篇 |
2015年 | 99篇 |
2014年 | 93篇 |
2013年 | 132篇 |
2012年 | 149篇 |
2011年 | 151篇 |
2010年 | 84篇 |
2009年 | 88篇 |
2008年 | 112篇 |
2007年 | 126篇 |
2006年 | 103篇 |
2005年 | 96篇 |
2004年 | 87篇 |
2003年 | 99篇 |
2002年 | 90篇 |
2001年 | 23篇 |
2000年 | 14篇 |
1999年 | 11篇 |
1998年 | 22篇 |
1997年 | 8篇 |
1996年 | 8篇 |
1995年 | 7篇 |
1994年 | 5篇 |
1993年 | 2篇 |
1992年 | 5篇 |
1990年 | 2篇 |
1989年 | 5篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1975年 | 4篇 |
1974年 | 2篇 |
1973年 | 5篇 |
1972年 | 2篇 |
1971年 | 2篇 |
1970年 | 2篇 |
1969年 | 2篇 |
1967年 | 1篇 |
1965年 | 1篇 |
1953年 | 1篇 |
排序方式: 共有1997条查询结果,搜索用时 31 毫秒
991.
Kirk R Laman H Knowles PP Murray-Rust J Lomonosov M Meziane el K McDonald NQ 《The Journal of biological chemistry》2008,283(32):22325-22335
F-box proteins are the substrate-recognition components of the Skp1-Cul1-F box protein (SCF) E3 ubiquitin ligases. Here we report a structural relationship between Fbxo7, a component of the SCF(Fbxo7) E3 ligase, and the proteasome inhibitor PI31. SCF(Fbxo7) is known to catalyze the ubiquitination of hepatoma-up-regulated protein (HURP) and the inhibitor of apoptosis (IAP) protein but also functions as an activator of cyclin D-Cdk6 complexes. We identify PI31 as an Fbxo7.Skp1 binding partner and show that this interaction requires an N-terminal domain present in both proteins that we term the FP (Fbxo7/PI31) domain. The crystal structure of the PI31 FP domain reveals a novel alpha/beta-fold. Biophysical and mutational analyses are used to map regions of the PI31 FP domain mediating homodimerization and required for heterodimerization with Fbxo7.Skp1. Equivalent mutations in Fbxo7 ablate interaction with PI31 and also block Fbxo7 homodimerization. Knockdown of Fbxo7 does not affect PI31 levels arguing against PI31 being a substrate for SCF(Fbxo7). We present a model for FP domain-mediated dimerization of SCF(Fbxo7) and PI31. 相似文献
992.
Mutations in the Drosophila mitochondrial tRNA amidotransferase, bene/gatA, cause growth defects in mitotic and endoreplicating tissues
下载免费PDF全文
![点击此处可从《Genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Morris JZ Bergman L Kruyer A Gertsberg M Guigova A Arias R Pogorzelska M 《Genetics》2008,178(2):979-987
Rapid larval growth is essential in the development of most metazoans. In this article, we show that bene, a gene previously identified on the basis of its oogenesis defects, is also required for larval growth and viability. We show that all bene alleles disrupt gatA, which encodes the Drosophila homolog of glutamyl-tRNA(Gln) amidotransferase subunit A (GatA). bene alleles are now referred to as gatA. GatA proteins are highly conserved throughout eukaryotes and many prokaryotes. These enzymes are required for proper translation of the proteins encoded by the mitochondrial genome and by many eubacterial genomes. Mitotic and endoreplicating tissues in Drosophila gatA loss-of-function mutants grow slowly and never achieve wild-type size, and gatA larvae die before pupariation. gatA mutant eye clones exhibit growth and differentiation defects, indicating that gatA expression is required cell autonomously for normal growth. The gatA gene is widely expressed in mitotic and endoreplicating tissues. 相似文献
993.
Ramensky VE Nurtdinov RN Neverov AD Mironov AA Gelfand MS 《American journal of human genetics》2008,83(1):94-98
Alternative splicing is a well-recognized mechanism of accelerated genome evolution. We have studied single-nucleotide polymorphisms and human-chimpanzee divergence in the exons of 6672 alternatively spliced human genes, with the aim of understanding the forces driving the evolution of alternatively spliced sequences. Here, we show that alternatively spliced exons and exon fragments (alternative exons) from minor isoforms experience lower selective pressure at the amino acid level, accompanied by selection against synonymous sequence variation. The results of the McDonald-Kreitman test suggest that alternatively spliced exons, unlike exons constitutively included in the mRNA, are also subject to positive selection, with up to 27% of amino acids fixed by positive selection. 相似文献
994.
995.
Potential for detecting changes in soil organic carbon concentrations resulting from climate change 总被引:4,自引:0,他引:4
The interaction between soil organic carbon pools and climate change is an important determinant of future atmospheric CO2 concentrations. Much effort has so far been allocated to manipulative process studies and predictive modelling exercises. Here, we examine the potential for directly detecting predicted changes through repeated soil sampling. Two contrasting benchmark plots were selected in the steppe at the Russian–Mongolian border, where soil organic carbon losses are predicted to be around 10% over the first 50 years of climate change. In both plots, 50 samples were taken to 20 and 30 cm depths. The estimated time intervals before re‐sampling by the same method that were likely to prove significant soil organic carbon losses (α=0.05; statistical power=0.90) were 43 and 26 years. 相似文献
996.
Extracellular Wnt ligands and their receptors of the Frizzled family control cell fate, proliferation, and polarity during metazoan development. Frizzled signaling modulates target gene expression through a beta-catenin-dependent pathway, functions to establish planar cell polarity in Drosophila epithelia, and activates convergent extension movements and intracellular Ca(2+) signaling in frog and fish embryos. Here, we report that a Frizzled receptor, Xenopus Frizzled 8 (Xfz8), activates c-Jun N-terminal kinases (JNK) and triggers rapid apoptotic cell death in gastrulating Xenopus embryos. This activity of Xfz8 required the cytoplasmic tail of the receptor and was blocked by a dominant inhibitor of JNK. Moreover, the cytoplasmic tail of Xfz8 targeted to the membrane was sufficient for activation of JNK and apoptosis. The apoptotic signaling was shared by a specific subset of Frizzled receptors, was inhibited by Wnt5a, and occurred in a Dishevelled- and T cell factor (TCF)-independent manner. Thus, our experiments identify a novel Frizzled-dependent signaling pathway, which involves JNK and differs from the beta-catenin-dependent and convergent extension pathways. 相似文献
997.
Steffen Lawo Mikhail Bashkurov Michael Mullin Mariana Gomez Ferreria Ralf Kittler Bianca Habermann Andrea Tagliaferro Ina Poser James R.A. Hutchins Björn Hegemann Deborah Pinchev Frank Buchholz Jan-Michael Peters Anthony A. Hyman Anne-Claude Gingras Laurence Pelletier 《Current biology : CB》2009,19(10):816-826
998.
999.
Roytberg Mikhail Gambin Anna Noe Laurent Lasota Slawomir Furletova Eugenia Szczurek Ewa Kucherov Gregory 《IEEE/ACM transactions on computational biology and bioinformatics / IEEE, ACM》2009,6(3):483-494
We apply the concept of subset seeds proposed in [1] to similarity search in protein sequences. The main question studied is the design of efficient seed alphabets to construct seeds with optimal sensitivity/selectivity trade-offs. We propose several different design methods and use them to construct several alphabets. We then perform a comparative analysis of seeds built over those alphabets and compare them with the standard Blastp seeding method [2], [3], as well as with the family of vector seeds proposed in [4]. While the formalism of subset seeds is less expressive (but less costly to implement) than the cumulative principle used in Blastp and vector seeds, our seeds show a similar or even better performance than Blastp on Bernoulli models of proteins compatible with the common BLOSUM62 matrix. Finally, we perform a large-scale benchmarking of our seeds against several main databases of protein alignments. Here again, the results show a comparable or better performance of our seeds versus Blastp. 相似文献
1000.
Kevin CR Kerr Sharon M Birks Mikhail V Kalyakin Yaroslav A Red'kin Eugeny A Koblik Paul DN Hebert 《Frontiers in zoology》2009,6(1):1-13