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651.
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
652.
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
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656.
Bonalume Neto R 《Nature》1999,402(6760):344-345
657.
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
658.
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
659.
Amin AR Attur MG Pillinger M Abramson SB 《Cellular and molecular life sciences : CMLS》1999,56(3-4):305-312
Recent studies have suggested that aspirin and aspirin-like compounds have a variety of actions in addition to their well-studied
ability to inhibit cyclooxygenases. These actions include inhibition of the uncoupling of oxidative phosphorylation, decreases
in adenosine triphosphate stores, increases in extracellular adenosine, downregulation of the expression and activity of inducible
nitric oxide synthetase, inhibition and/or stimulation of various mitogen-activated protein kinase activities and inhibition
of nuclear factor binding κB site (NF-κB) activation. Moreover, aspirin-like compounds have recently been shown to have previously
unappreciated clinical and biological effects, some apparently independent of cyclooxygenase. In this review we discuss the
various mechanisms of action of aspirin-like compounds and their relevance to clinical disease and therapy.
Received 1 February 1999; received after revision 1 April 1999; accepted 7 May 1999 相似文献
660.
Favatier F Jacquier-Sarlin MR Swierczewski E Polla BS 《Cellular and molecular life sciences : CMLS》1999,56(7-8):701-708
A bi-allelic polymorphism found in the regulatory region of the human heat shock (HS) protein (HSP) hsp70-1 gene, which comprises an A-->C transversion, 3 bp upstream of the HS element (HSE), has been associated with extended HLA haplotypes. In view of the chaperoning and protective functions of Hsp70, we investigated whether this hsp70-1 bi-allelic polymorphism could modulate the stress response, which may relate to enhanced resistance or susceptibility to certain diseases. We compared the basal and HS-induced HS factor (HSF)-binding activity of the two polymorphic HSEs, hsp70-1 mRNA accumulation and HSP expression in two human Epstein Barr virus (EBV)-transformed B cell lines typed for hsp70-1 promoter alleles. Our results suggest that hsp70-1 promoter polymorphism does not influence HSF-binding activity, hsp70 mRNA accumulation or synthesis in human EBV-transformed B cell lines. 相似文献