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The influence of ionic strength and composition on the binding and inhibition of human leukocyte elastase by glycosaminoglycans with variable degree and position of sulfation was investigated. The kinetic mechanism of inhibition had a hyperbolic, mixed-type character with a competitive component that was promoted by low ionic strength, reduced by phosphate ions, and which also depended on the substrate and glycosaminoglycan structure. Enzyme binding was a cooperative phenomenon that varied with ionic strength and composition. The inhibition patterns correlated with the cationic character of elastase and with the distribution of arginines on its molecular surface, most notably with residues located in the vicinity of the substrate binding region. The order of affinity for elastase binding was chondroitin 4-sulfate < chondroitin 6-sulfate < dermatan sulfate, iduronate-containing derivatives being superior with respect to the glucuronate-containing counterparts. Additional sulfation at both the 4- and 6- positions or at the N- and 4-positions of the N-acetylgalactosamine moiety decidedly improved the inhibitory efficiency. The results highlight a fundamental physiological role of enzyme-glycosaminoglycan interactions. In the azurophil granule of the human polymorphonuclear neutrophil, elastase and other enzymes are bound to a matrix of chondroitin 4-sulfate because this is the only glycosaminoglycan that simultaneously offers good binding for enzyme compartmentalization together with prompt release from the bound state at the onset of phagocytosis.  相似文献   
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裂缝性油气藏采收率:100个裂缝性油气田实例的经验总结   总被引:5,自引:2,他引:3  
通过对世界上100个裂缝性油气藏的综合评价,研究储集层及流体本身的性质(包括孔隙度、渗透率、黏度、可动油比例、含水饱和度、润湿性及裂缝分布特征等)和驱动机制及油藏管理战略(优化日产量和采用不同类型的提高采收率技术)对其最终采收率的影响。将裂缝性油气藏分为4类:I类的基质几乎没有孔隙度和渗透率,裂缝是储存空间和流体流动的通道;Ⅱ类的基质有较低的孔隙度和渗透率,基质提供储存空间,裂缝提供流动通道;Ⅲ类(微孔隙)的基质具有高孔隙度和低渗透率,基质提供储存空间,裂缝提供流动通道;Ⅳ类(大孔隙)的基质具有高的孔隙度和渗透率,基质提供储存空间和流动通道,裂缝仅增加渗透率。对26个Ⅱ类油气藏和20个Ⅲ类油气藏的开采历史的研究表明:Ⅱ类油气藏的采收率受水驱强度和最优日产量控制,日产量过高会很容易破坏Ⅱ类油气藏,一些Ⅱ类油气藏如果管理得当,采收率可以很高,不需要二次或三次采油;Ⅲ类油气藏的采收率主要受岩石和流体本身性质的影响,特别是基质渗透率、流体重度、润湿性以及裂缝强度等,不进行二次或三次采油不可能完全开采,往往需要采用一些提高采收率的专门技术。以往将Ⅱ类和Ⅲ类裂缝性油气藏归为一类,认识它们的区别将有助于选择更好的开发策略。  相似文献   
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Specific binding of the plasmid-encoded protein, TrfA, and the Escherichia coli DnaA protein to the origin region (oriV) is required for the initiation of replication of the broad host range plasmid RK2. It has been shown that the DnaA protein which binds to DnaA boxes upstream of the TrfA-binding sites (iterons) cannot by itself form an open complex, but it enhances the formation of the open complex by TrfA (Konieczny, I., Doran, K. S., Helinski, D. R., Blasina, A. (1997) J. Biol. Chem. 272, 20173). In this study an in vitro replication system is reconstituted from purified TrfA protein and E. coli proteins. With this system, a specific interaction between the DnaA and DnaB proteins is required for delivery of the helicase to the RK2 origin region. Although the DnaA protein directs the DnaB-DnaC complex to the plasmid replication origin, it cannot by itself activate the helicase. Both DnaA and TrfA proteins are required for DnaB-induced template unwinding. We propose that specific changes in the nucleoprotein structure mediated by TrfA result in a repositioning of the DnaB helicase within the open origin region and an activation of the DnaB protein for template unwinding.  相似文献   
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Peripheral benzodiazepine receptors (PBRs) are expressed in a variety of tissues but are normally found at low levels in the brain. Following various types of nerve injury, a reactive gliosis results that exhibits a high expression of this receptor. To further characterize the expression of PBRs following neuronal injury, we evaluated PBR expression in the facial nucleus following facial nerve axotomy (FNA). Injury to a peripheral nerve results in a complex series of metabolic and morphological changes around the injured neuron. Transections of the facial nerve results in a rapid activation of both astrocytes and microglia around axotomized motor neurons. FNA resulted in an increase in the staining for both astrocytes (glial fibrillary acidic protein) and activated microglia (OX42). There was also a reduction in synaptic contacts with the motor nucleus as evidenced by reduced staining for the synaptic marker, synaptophysin. In sections labeled with [3H]-PK11195, the subsequent autoradiograms displayed marked increases in the labeling for PBRs. This increase was observed at 5, 7 and 10 days after nerve transection. The increase was primarily in the level of expression (Bmax), with no change in the affinity of the ligand (Kd). The increase in PBR expression after FNA supports the hypothesis that PBRs can be used as a sensitive marker for CNS injury.  相似文献   
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The presence of nitric oxide synthase (NO-synthase), the enzyme responsible for the production of nitric oxide (NO) from L-arginine, is shown immunocytochemically in the intrinsic neurons of the human and porcine respiratory tract. NO-synthase immunoreactivity is demonstrated in a subpopulation of neurons of the microganglia present in the wall of the extra- and intrapulmonary bronchi as well as in the hilar region of the lung in relation to blood vessels. The immunostaining was also found in some nerve fibers of the respiratory nervous system. Human and porcine lung gave similar results. The possible involvement of NO in the nonadrenergic noncholinergic (NANC) nervous regulation of the lung is discussed.  相似文献   
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The ability of antiviral and antiretroviral drugs to enter the brain is a critical issue in the treatment of many viral brain diseases, including HIV-related neurologic disease. Much of the literature concerning nucleoside analog entry into the nervous system focuses on drug levels in the cerebrospinal fluid (CSF), equating these with drug levels in the brain extracellular fluid (ECF) as though the two compartments intermix freely. We review the anatomic and physiologic aspects of drug entry into CSF and into brain ECF, as well as the exchange processes between these two compartments. In most instances drug concentrations in the CSF and ECF compartments bear little relationship to one another and using CSF concentrations to extrapolate brain ECF concentrations may significantly overestimate the latter. Accepted terminology and methodology for making measurements of blood-brain barrier function are discussed. Studies of brain uptake that express results as brain:plasma ratios, or that have used microdialysis, may overestimate the amount of drug reaching the brain. Using published data, we present an estimate of the time course of Zidovudine (AZT) concentrations in brain ECF and show that brain concentrations of AZT will likely be below that necessary to inhibit HIV-1 replication when AZT is administered systemically. Antiviral nucleosides and oligonucleotides appear to have limited entry into the brain when given systemically, which may hinder therapy of viral brain diseases, while some of the protease inhibitors may enter the brain more readily. Alternative methods for increasing antiviral and antiretroviral drug delivery to brain are discussed.  相似文献   
9.
D.A. Allan  P.J. Smith  J.A. Bowie 《Vacuum》1985,35(12):543-546
The gates of GaAs MESFETS rely on the formation of a Schottky diode between the semiconductor surface and a deposited metal and so are extremely sensitive to the nature of this interface. For this reason an investigation of surface damage and contamination by the various processing stages involved in IC fabrication has been undertaken. This paper outlines the results obtained from processes involved in activation of ion implantation through annealing with a dielectric encapsulant, wet chemical etching, and metallization. Methods for removing or minimizing the effects of processing damage or contamination are also investigated.  相似文献   
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