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901.
PO Freskgard LC Petersen DA Gabriel X Li E Persson 《Canadian Metallurgical Quarterly》1998,37(20):7203-7212
The binding of the multidomain protein factor VIIa (fVIIa) to tissue factor provides the interprotein communication necessary to make fVIIa an efficient catalyst of the initial event in the extrinsic pathway of blood coagulation. We have investigated the stability of individual domains in fVIIa and the influence of Ca2+ and an irreversible active-site inhibitor (FFR-chloromethyl ketone). Equilibrium guanidine hydrochloride (GuHCl)-induced unfolding monitored by tryptophan fluorescence and far-UV circular dichroism (CD) demonstrated that the gamma-carboxyglutamic acid (Gla) domain unfolds at 0.3 M GuHCl and the serine protease (SP) domain at 3 M GuHCl and that Ca2+ is a prerequisite for the formation of an ordered, compact structure in the Gla domain. The loss of amidolytic activity coincides with the first transition, which is stabilized by the active-site inhibitor, and a change in the environment of the active site is demonstrated using a fluorescent inhibitor (DEGR-chloromethyl ketone). Thermal unfolding monitored by differential scanning calorimetry (DSC) reveals that Ca2+ stabilizes the SP domain slightly, increasing the unfolding temperature by 2.7 degrees C. In addition, Ca2+ is required for a large enthalpy change concomitant with unfolding of the Gla domain, and this unfolding enthalpy is only detectable in the presence of the SP domain, indicating some kind of interaction between these domains. Thermal unfolding measured by CD indicates secondary structural changes at the same temperature as the heat absorption in the DSC but only when both the Gla domain and the SP domain are present together with Ca2+ ions. Taken together, these results indicate a Ca2+-dependent interaction between the Gla domain and the SP domain, implying a high degree of flexibility of the domains in free fVIIa. It is also shown that the epidermal growth factor-like domains are stable at elevated temperatures and high GuHCl concentrations. Moreover, already at physiological temperature, subtle structural changes take place which influence the overall shape of fVIIa and are detrimental to its enzymatic activity. 相似文献
902.
高韧性—70℃低温钢WHD4(09MnNiDR)的性能及应用 总被引:1,自引:0,他引:1
本文研究了武钢研制生产的高韧性—70℃低温钢WHD4(09MnNiDR)钢板的全面力学性能、焊接性能.介绍该钢在大型石油、化工设备中的应用实例.结果表明该钢具有优异的低温韧性和优良的焊接性能,是制造低温压力容器等设备的理想用材. 相似文献
903.
904.
Actor模型是一种面向对象的并发模型,但它缺乏对继承机制的支持。本文试图阐明在Actor模型中该支持什么样的继承以及如何支持这种继承。 相似文献
905.
Mechanical properties of Al2O3 particle-Y-TZP matrix composite and its toughening mechanism 总被引:6,自引:0,他引:6
Dense Al2O3 particle-Y-TZP matrix (Al2O3<40 vol%) composite was prepared by pressureless sintering at 1550°C. Composites with 10–30 vol% Al2O3 particles showed enhanced fracture toughness, bending strength and Vicker's hardness as compared to single-phase Y-TZP. The highest strength (1150 MPa) and highest toughness (12.4 MPa m1/2) were obtained for the composite containing 10 vol% Al2O3. It was found that, in addition to the contribution by the crack-deflection effect, the enhanced phase transformation from tetragonal to monoclinic during fracture was the main toughening mechanism in operation in the composites. 相似文献
906.
Composite generation and transmission system expansion analysis should take into account both economic considerations and adequacy requirements. An optimum expansion plan should achieve the minimum total investment, operation and damage cost. A minimum cost assessment method for composite system expansion planning, which can be used to consider generation expansion and transmission expansion simultaneously, is presented. The minimization model proposed to incorporate both operating and outage costs can recognize different customer damage functions at different load buses and includes the duration of the simulated contingency system states . A computer program based on the presented method has been developed to provide a set of line, load bus, generator bus and system indices which can be used to select optimal expansion plans at different load growth levels. Case studies in which the method is applied to the IEEE Modified Reliability Test System indicate its effectiveness 相似文献
907.
新型后坐加速度开关阵列传感器 总被引:1,自引:0,他引:1
分析了国外后坐加速度传感器发展动向。介绍了新型后坐加速度开关阵列传感器的结构、原理、参数选择和性能设计。给出了原理性静态、动态试验结果,以证明新方案的可行性。最后指出了这种新型结构的传感器所具有的特点。 相似文献
908.
C Martel L Provencher X Li A St Pierre G Leblanc S Gauthier Y Mérand F Labrie 《Canadian Metallurgical Quarterly》1998,64(3-4):199-205
Tamoxifen (TAM), the only antiestrogen currently available for the endocrine therapy of breast cancer behaves as a mixed agonist/antagonist of estrogen action, thus limiting its therapeutic potential. We report the binding characteristics of a novel series of nonsteroidal antiestrogens to the rat uterine estrogen receptor. As measured by competition studies, the affinity of EM-652, the active metabolite of the prodrug EM-800, for the estrogen receptor is 7-11 times higher than that of 17beta-estradiol (E2), ICI 182780, and hydroxy-tamoxifen (OH-TAM), the active metabolite of Tamoxifen. EM-652 is 20x more potent than ICI 164384 and Droloxifene while it is 400 times more potent than Toremifene in displacing [3H]E2 from the rat uterine estrogen receptor. On the other hand, the prodrug EM-800 and Tamoxifen have respectively 150-fold and 410-fold less affinity for the estrogen receptor than the pure antiestrogen EM-652. No significant binding of EM-652, EM-800, TAM or OH-TAM was observed to the rat uterine progesterone receptor at concentrations up to 10,000 nM except for TAM that caused a 50% displacement of labeled R5020 at 4000 nM. No significant binding of EM-652 or EM-800 was observed on the rat ventral prostate androgen receptor or the rat uterine progesterone receptor. The present data demonstrate the high affinity and specificity of the new antiestrogen, EM-652, for the rat uterine estrogen receptor. The antiestrogen EM-652 thus becomes the compound having the highest known affinity for the estrogen receptor. Due to its unique potency and its pure antiestrogenic activity already demonstrated in many systems, this antiestrogen could well offer an important advance for the endocrine therapy of breast cancer, uterine cancer, and other estrogen-sensitive diseases in women. 相似文献
909.
Adducin is a heteromeric protein with subunits containing a COOH-terminal myristoylated alanine-rich C kinase substrate (MARCKS)-related domain that caps and preferentially recruits spectrin to the fast-growing ends of actin filaments. The basic MARCKS-related domain, present in alpha, beta, and gamma adducin subunits, binds calmodulin and contains the major phosphorylation site for protein kinase C (PKC). This report presents the first evidence that phosphorylation of the MARCKS-related domain modifies in vitro and in vivo activities of adducin involving actin and spectrin, and we demonstrate that adducin is a prominent in vivo substrate for PKC or other phorbol 12-myristate 13-acetate (PMA)-activated kinases in multiple cell types, including neurons. PKC phosphorylation of native and recombinant adducin inhibited actin capping measured using pyrene-actin polymerization and abolished activity of adducin in recruiting spectrin to ends and sides of actin filaments. A polyclonal antibody specific to the phosphorylated state of the RTPS-serine, which is the major PKC phosphorylation site in the MARCKS-related domain, was used to evaluate phosphorylation of adducin in cells. Reactivity with phosphoadducin antibody in immunoblots increased twofold in rat hippocampal slices, eight- to ninefold in human embryonal kidney (HEK 293) cells, threefold in MDCK cells, and greater than 10-fold in human erythrocytes after treatments with PMA, but not with forskolin. Thus, the RTPS-serine of adducin is an in vivo phosphorylation site for PKC or other PMA-activated kinases but not for cAMP-dependent protein kinase in a variety of cell types. Physiological consequences of the two PKC phosphorylation sites in the MARCKS-related domain were investigated by stably transfecting MDCK cells with either wild-type or PKC-unphosphorylatable S716A/S726A mutant alpha adducin. The mutant alpha adducin was no longer concentrated at the cell membrane at sites of cell-cell contact, and instead it was distributed as a cytoplasmic punctate pattern. Moreover, the cells expressing the mutant alpha adducin exhibited increased levels of cytoplasmic spectrin, which was colocalized with the mutant alpha adducin in a punctate pattern. Immunofluorescence with the phosphoadducin-specific antibody revealed the RTPS-serine phosphorylation of adducin in postsynaptic areas in the developing rat hippocampus. High levels of the phosphoadducin were detected in the dendritic spines of cultured hippocampal neurons. Spectrin also was a component of dendritic spines, although at distinct sites from the ones containing phosphoadducin. These data demonstrate that adducin is a significant in vivo substrate for PKC or other PMA-activated kinases in a variety of cells, and that phosphorylation of adducin occurs in dendritic spines that are believed to respond to external signals by changes in morphology and reorganization of cytoskeletal structures. 相似文献
910.