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1.
The endosomal sorting complexes required for transport (ESCRT) pathway drives reverse topology membrane fission events within multiple cellular pathways, including cytokinesis, multivesicular body biogenesis, repair of the plasma membrane, nuclear membrane vesicle formation, and HIV budding. The AAA ATPase Vps4 is recruited to membrane necks shortly before fission, where it catalyzes disassembly of the ESCRT-III lattice. The N-terminal Vps4 microtubule-interacting and trafficking (MIT) domains initially bind the C-terminal MIT-interacting motifs (MIMs) of ESCRT-III subunits, but it is unclear how the enzyme then remodels these substrates in response to ATP hydrolysis. Here, we report quantitative binding studies that demonstrate that residues from helix 5 of the Vps2p subunit of ESCRT-III bind to the central pore of an asymmetric Vps4p hexamer in a manner that is dependent upon the presence of flexible nucleotide analogs that can mimic multiple states in the ATP hydrolysis cycle. We also find that substrate engagement is autoinhibited by the Vps4p MIT domain and that this inhibition is relieved by binding of either Type 1 or Type 2 MIM elements, which bind the Vps4p MIT domain through different interfaces. These observations support the model that Vps4 substrates are initially recruited by an MIM-MIT interaction that activates the Vps4 central pore to engage substrates and generate force, thereby triggering ESCRT-III disassembly.  相似文献   
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植物对UV-B辐射增强应答的分子机制及信号级联研究进展   总被引:1,自引:0,他引:1  
地表的UV-B辐射量伴随着大气平流层臭氧层的变薄而不断增强,给地球生态系统带来严重影响.UV-B主要通过抑制植物光合作用、伤害生物膜及DNA等生物大分子来影响其生长发育,最终导致生物量及产量降低,甚至致死.植物在进化过程中形成了自我防护及防御机制,如DNA损伤的自我修复,活性氧自由基的酶促及非酶促清除机制,以及紫外吸收物质的诱导合成等;同时,在植物中也有许多物质及不同途径来感受和应答UV-B胁迫.本文从UV-B辐射增强对植物造成损伤的主要途径、植物对UV-B辐射增强的应答机制及信号级联过程等方面的研究进展进行综述.  相似文献   
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Myxovirus resistance (Mx) GTPases are induced by interferon and inhibit multiple viruses, including influenza and human immunodeficiency viruses. They have the characteristic domain architecture of dynamin-related proteins with an N-terminal GTPase (G) domain, a bundle signaling element, and a C-terminal stalk responsible for self-assembly and effector functions. Human MxA (also called MX1) is expressed in the cytoplasm and is partly associated with membranes of the smooth endoplasmic reticulum. It shows a protein concentration-dependent increase in GTPase activity, indicating regulation of GTP hydrolysis via G domain dimerization. Here, we characterized a panel of G domain mutants in MxA to clarify the role of GTP binding and the importance of the G domain interface for the catalytic and antiviral function of MxA. Residues in the catalytic center of MxA and the nucleotide itself were essential for G domain dimerization and catalytic activation. In pulldown experiments, MxA recognized Thogoto virus nucleocapsid proteins independently of nucleotide binding. However, both nucleotide binding and hydrolysis were required for the antiviral activity against Thogoto, influenza, and La Crosse viruses. We further demonstrate that GTP binding facilitates formation of stable MxA assemblies associated with endoplasmic reticulum membranes, whereas nucleotide hydrolysis promotes dynamic redistribution of MxA from cellular membranes to viral targets. Our study highlights the role of nucleotide binding and hydrolysis for the intracellular dynamics of MxA during its antiviral action.  相似文献   
4.
Substituted enzyme (or ping-pong) mechanisms usually involve enzymes that exist in two forms that alternate during the catalytic reaction. A method is described here for determining the position of the equilibrium of a half reaction in a ping-pong enzyme mechanism that is based on the kinetics of the burst reaction which occurs upon addition of reactants that recycle the enzyme from one form to another. The theoretical basis for the analysis is developed, and the method is applied to the half reaction of the aldimine form of aspartate transaminase with difluoro-oxaloacetate. Special issue dedicated to Herman Bachelard  相似文献   
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Sensitivity of North American sturgeons and paddlefish to fishing mortality   总被引:1,自引:0,他引:1  
Sturgeons and paddlefish exhibit unusual combinations of morphology, habits, and life history characteristics, which make them highly vulnerable to impacts from human activities, particularly fisheries. Five North American sturgeons (shortnose, Gulf, pallid, Alabama, and green sturgeon) are listed as endangered or threatened by management authorities. Managers have instituted fishery closures for the three other species of North American sturgeons (Atlantic, white, and shovelnose) and paddlefish because of low stock abundance at some point in this century. Reproductive potential in four species I examined (Atlantic, white, and shortnose sturgeon, and paddlefish) is more sensitive to fishing mortality than it is for three other intensively-fished coastal species in North America: striped bass, winter flounder, and bluefish. The sturgeons and paddlefish are generally longer-lived than the three other coastal species, and also have an older age at full maturity, lower maximum fecundity values, and older ages at which 50% of the lifetime egg production is realized with no fishing mortality.  相似文献   
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对中甸刺玫Rosa praelucens种子结构及其透水性,赤霉素处理对胚的影响,果壳、种皮、胚乳的粗提物活性进行研究。结果表明:(1) 中甸刺玫外种皮是由多层排列紧密的厚壁细胞组成,内种皮为坚硬致密的栅栏组织;(2) 种皮对种子的吸胀阻碍较大, 未处理的种子吸水率较低,吸水13 d后增加量为18.82%;(3) 果实结籽率为0.69%,多数果实中没有饱满的种子;(4) 赤霉素100 mg·kg-1预处理种子可加快胚的萌发速率;(5) 胚乳、种皮、果壳中存在内源抑制物。中甸刺玫种子的休眠是由其形态和生理特点引起的综合休眠。  相似文献   
10.
Statins, with their lipid-lowering properties, are a first-line therapy for the prevention of cardiovascular diseases. Recent evidence, however, suggests that statins can increase the risk of new-onset diabetes (NOD). The molecular mechanisms of statin-induced NOD are not precisely known, although some pathophysiologic mechanisms have been suggested. Specific to the beta cell, these mechanisms include alterations in insulin secretion, changes in ion channels, modulation of signaling pathways, and inflammation/oxidative stress. Outwith the beta cell, other suggested mechanisms involve adipocytes, including alterations in adipocyte differentiation and modulation of leptin and adiponectin, and genetic and epigenetic mechanisms, including alterations in microRNA. The evidence supporting these and other mechanisms will be discussed. Greater understanding of the underlying mechanisms linking the onset of diabetes to statin therapy is essential and clinically relevant, as it may enable novel preventative or therapeutic approaches to be instituted and guide the production of a new generation of statins lacking this side effect.  相似文献   
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