全文获取类型
收费全文 | 28514篇 |
免费 | 86篇 |
国内免费 | 75篇 |
专业分类
系统科学 | 280篇 |
丛书文集 | 507篇 |
教育与普及 | 49篇 |
理论与方法论 | 113篇 |
现状及发展 | 12645篇 |
研究方法 | 1148篇 |
综合类 | 13484篇 |
自然研究 | 449篇 |
出版年
2013年 | 195篇 |
2012年 | 428篇 |
2011年 | 876篇 |
2010年 | 170篇 |
2008年 | 463篇 |
2007年 | 514篇 |
2006年 | 548篇 |
2005年 | 533篇 |
2004年 | 542篇 |
2003年 | 504篇 |
2002年 | 438篇 |
2001年 | 858篇 |
2000年 | 813篇 |
1999年 | 501篇 |
1992年 | 499篇 |
1991年 | 431篇 |
1990年 | 469篇 |
1989年 | 383篇 |
1988年 | 426篇 |
1987年 | 447篇 |
1986年 | 394篇 |
1985年 | 567篇 |
1984年 | 437篇 |
1983年 | 369篇 |
1982年 | 300篇 |
1981年 | 310篇 |
1980年 | 406篇 |
1979年 | 880篇 |
1978年 | 747篇 |
1977年 | 708篇 |
1976年 | 571篇 |
1975年 | 653篇 |
1974年 | 853篇 |
1973年 | 727篇 |
1972年 | 771篇 |
1971年 | 875篇 |
1970年 | 1162篇 |
1969年 | 916篇 |
1968年 | 795篇 |
1967年 | 836篇 |
1966年 | 770篇 |
1965年 | 573篇 |
1964年 | 163篇 |
1959年 | 304篇 |
1958年 | 468篇 |
1957年 | 349篇 |
1956年 | 302篇 |
1955年 | 272篇 |
1954年 | 305篇 |
1948年 | 207篇 |
排序方式: 共有10000条查询结果,搜索用时 278 毫秒
911.
A structural change in the kinesin motor protein that drives motility 总被引:34,自引:0,他引:34
Rice S Lin AW Safer D Hart CL Naber N Carragher BO Cain SM Pechatnikova E Wilson-Kubalek EM Whittaker M Pate E Cooke R Taylor EW Milligan RA Vale RD 《Nature》1999,402(6763):778-784
Kinesin motors power many motile processes by converting ATP energy into unidirectional motion along microtubules. The force-generating and enzymatic properties of conventional kinesin have been extensively studied; however, the structural basis of movement is unknown. Here we have detected and visualized a large conformational change of an approximately 15-amino-acid region (the neck linker) in kinesin using electron paramagnetic resonance, fluorescence resonance energy transfer, pre-steady state kinetics and cryo-electron microscopy. This region becomes immobilized and extended towards the microtubule 'plus' end when kinesin binds microtubules and ATP, and reverts to a more mobile conformation when gamma-phosphate is released after nucleotide hydrolysis. This conformational change explains both the direction of kinesin motion and processive movement by the kinesin dimer. 相似文献
912.
Prion diseases can be infectious, sporadic and genetic. The infectious forms of these diseases, including bovine spongiform encephalopathy and Creutzfeldt-Jakob disease, are usually characterized by the accumulation in the brain of the transmissible pathogen, an abnormally folded isoform of the prion protein (PrP) termed PrPSc. However, certain inherited PrP mutations appear to cause neurodegeneration in the absence of PrPSc, working instead by favoured synthesis of CtmPrP, a transmembrane form of PrP. The relationship between the neurodegeneration seen in transmissible prion diseases involving PrPSc and that associated with ctmPrP has remained unclear. Here we find that the effectiveness of accumulated PrPSc in causing neurodegenerative disease depends upon the predilection of host-encoded PrP to be made in the ctmPrP form. Furthermore, the time course of PrPSc accumulation in transmissible prion disease is followed closely by increased generation of CtmPrP. Thus, the accumulation of PrPSc appears to modulate in trans the events involved in generating or metabolising CtmPrP. Together, these data suggest that the events of CtmPrP-mediated neurodegeneration may represent a common step in the pathogenesis of genetic and infectious prion diseases. 相似文献
913.
In metazoans, spliceosome assembly is initiated through recognition of the 5' splice site by U1 snRNP and the polypyrimidine tract by the U2 small nuclear ribonucleoprotein particle (snRNP) auxiliary factor, U2AF. U2AF is a heterodimer comprising a large subunit, U2AF65, and a small subunit, U2AF35. U2AF65 directly contacts the polypyrimidine tract and is required for splicing in vitro. In comparison, the role of U2AF35 has been puzzling: U2AF35 is highly conserved and is required for viability, but can be dispensed with for splicing in vitro. Here we use site-specific crosslinking to show that very early during spliceosome assembly U2AF35 directly contacts the 3' splice site. Mutational analysis and in vitro genetic selection indicate that U2AF35 has a sequence-specific RNA-binding activity that recognizes the 3'-splice-site consensus, AG/G. We show that for introns with weak polypyrimidine tracts, the U2AF35-3'-splice-site interaction is critical for U2AF binding and splicing. Our results demonstrate a new biochemical activity of U2AF35, identify the factor that initially recognizes the 3' splice site, and explain why the AG dinucleotide is required for the first step of splicing for some but not all introns. 相似文献
914.
915.
916.
917.
Bonalume Neto R 《Nature》1999,402(6760):344-345
918.
Bacterial suicide through stress 总被引:9,自引:0,他引:9
Outside of the laboratory, bacterial cells are constantly exposed to stressful conditions, and an ability to resist those
stresses is essential to their survival. However, the degree of stress required to bring about cell death varies with growth
phase, amongst other parameters. Exponential phase cells are significantly more sensitive to stress than stationary phase
ones, and a novel hypothesis has recently been advanced to explain this difference in sensitivity, the suicide response. Essentially,
the suicide response predicts that rapidly growing and respiring bacterial cells will suffer growth arrest when subjected
to relatively mild stresses, but their metabolism will continue: a burst of free-radical production results from this uncoupling
of growth from metabolism, and it is this free-radical burst that is lethal to the cells, rather than the stress per se. The
suicide response hypothesis unifies a variety of previously unrelated empirical observations, for instance induction of superoxide
dismutase by heat shock, alkyl-hydroperoxide reductase by osmotic shock and catalase by ethanol shock. The suicide response
also has major implications for current [food] processing methods.
Received 29 March 1999; received after revision 14 May 1999; accepted 17 May 1999 相似文献
919.
At the end of mitosis, daughter cells are separated from each other by cytokinesis. This process involves equal partitioning
and segregation of cytoplasm between the two cells. Despite years of study, the mechanism driving cytokinesis in animal cells
is not fully understood. Actin and myosin are major components of the contractile ring, the structure at the equator between
the dividing cells that provides the force necessary to constrict the cytoplasm. Despite this, there are also tantalizing
results suggesting that cytokinesis can occur in the absence of myosin. It is unclear what the roles are of the few other
contractile ring components identified to date. While it has been difficult to identify important proteins involved in cytokinesis,
it has been even more challenging to pinpoint the regulatory mechanisms that govern this vital process. Cytokinesis must be
precisely controlled both spatially and temporally; potential regulators of these parameters are just beginning to be identified.
This review discusses the recent progress in our understanding of cytokinesis in animal cells and the mechanisms that may
regulate it.
Received 24 August 1998; received after revision 9 October 1998; accepted 9 October 1998 相似文献
920.
M. Pucéat 《Cellular and molecular life sciences : CMLS》1999,55(10):1216-1229
Intracellular pH (pHi) is a major regulator of various and critical cellular functions. A close regulation of pHi is thus mandatory to maintain normal cellular activity. To this end, all cells express ion transporters that carry across
their plasma membrane H+ or equivalent H+ into and out of the cell. Besides pHi, these ion transporters are under the regulation of neurohormonal stimuli. This review summarises the molecular identity,
regulation and function of the main membrane pH-regulatory ion transporters.
Received 30 December 1998; received after revision 4 February 1999; accepted 9 February 1999 相似文献