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381.
W T Clusin 《Nature》1983,301(5897):248-250
Electrical excitation of cardiac muscle may sometimes be due to initiation of inward current by the presence of Ca2+ ions at the inner surface of the cell membrane. During digitalis toxicity and other conditions that abnormally augment cellular Ca2+ stores, premature release of Ca2+ from the sarcoplasmic reticulum leads to a transient inward current, which is large enough to initiate premature beats and is accompanied by a transient contractile response. This inward current may be mediated either by electrogenic sodium-calcium exchange or by specific Ca2+-activated cation channels that have recently been characterized in tissue cultures of cardiac myocytes. An obvious question raised by these observations is whether release of the sequestered Ca2+ stores during each normal beat exerts a similar influence on membrane potential. To explore this, chick embryonic myocardial cell aggregates were voltage-clamped during abrupt exposure to caffeine, which is known to release Ca2+ from the sarcoplasmic reticulum. The speed of the perfusion system and the relative absence of diffusion barriers in the tissue-cultured cells allowed the effects of caffeine-induced Ca2+ release to be studied on a time scale comparable to that of a single normal beat. We report here that abrupt exposure of the cells to caffeine produced a transient inward current having similar features to that of digitalis toxicity, and which was both large enough and rapid enough to potentially contribute to the action potential. 相似文献
382.
Structure of an adenine-cytosine base pair in DNA and its implications for mismatch repair 总被引:30,自引:0,他引:30
Mutational pathways rely on introducing changes in the DNA double helix. This may be achieved by the incorporation of a noncomplementary base on replication or during genetic recombination, leading to substitution mutation. In vivo studies have shown that most combinations of base-pair mismatches can be accommodated in the DNA double helix, albeit with varying efficiencies. Fidelity of replication requires the recognition and excision of mismatched bases by proofreading enzymes and post-replicative mismatch repair systems. Rates of excision vary with the type of mismatch and there is some evidence that these are influenced by the nature of the neighbouring sequences. However, there is little experimental information about the molecular structure of mismatches and their effect on the DNA double helix. We have recently determined the crystal structures of several DNA fragments with guanine X thymine and adenine X guanine mismatches in a full turn of a B-DNA helix and now report the nature of the base pairing between adenine and cytosine in an isomorphous fragment. The base pair found in the present study is novel and we believe has not previously been demonstrated. Our results suggest that the enzymatic recognition of mismatches is likely to occur at the level of the base pairs and that the efficiency of repair can be correlated with structural features. 相似文献
383.
384.
Structure of pre-pro-von Willebrand factor and its expression in heterologous cells 总被引:30,自引:0,他引:30
D T Bonthron R I Handin R J Kaufman L C Wasley E C Orr L M Mitsock B Ewenstein J Loscalzo D Ginsburg S H Orkin 《Nature》1986,324(6094):270-273
Von Willebrand factor (vWF), a multifunctional haemostatic glycoprotein derived from endothelial cells and megakaryocytes, mediates platelet adhesion to injured subendothelium and binds coagulation factor VIII in the circulation. Native vWF is a disulphide-bonded homopolymer; the monomeric subunits, of apparent relative molecular mass (Mr) 220,000 (220K) are derived from an intracellular precursor estimated at 260-275K. Multimer assembly is preceded by the formation of dimers, linked near their C-termini, which then assemble into filamentous polymers. The importance of the removal of the large vWF pro-polypeptide during multimer assembly, and whether this or other stages of the complex post-translational processing require components specific to endothelial cells or megakaryocytes, is unknown. Here we report an analysis of the complete sequence of pre-pro-vWF and expression of the molecule in heterologous cells. The vWF precursor is composed of several repeated subdomains. When expressed in COS and CHO cells, it is cleaved and assembled into biologically active high relative molecular mass disulphide bonded multimers. This suggests that the information for assembly of this complex molecule resides largely within its primary structure. 相似文献
385.
In several rat models, including those with circular and semicircular rectal aganglionosis, the rectosphincteric reflex was examined. The reflex was confirmed to be essentially an intramural one and its route is considered to run mainly in the longitudinal and partly in the oblique directions. 相似文献
386.
Y. Mizushima T. Harauchi T. Yoshizaki S. Makino 《Cellular and molecular life sciences : CMLS》1984,40(4):359-361
Summary A colony of Wistar rats with a hereditary defect in L-ascorbic acid-synthesizing ability was established. This rat, like primates and guinea pigs, lacks L-gulonolactone oxidase (EC 1.1.3.8) which catalyzes the last step of L-ascorbic acid biosynthesis. When L-ascorbic acid was added to their drinking water, the rats grew almost normally and were fertile. These mutant rats should be useful not only for nutritional and parmacological studies on vitamin C but also for genetic studies on the lack of this enzyme.Acknowledgments. We are indebted to K. Katagiri, the previous director of Aburahi Laboratories, for his encouragement during the experiment. We are also grateful to H. Nishimura, Professor Emeritus of Kyoto University, and Y. Hasegawa of our laboratory for their helpful suggestions. 相似文献
387.
Determination of polyamine oxidase activities in human tissues 总被引:2,自引:0,他引:2
A very simple fluorometric assay for polyamine oxidase (PAO) in tissues, with N1-monoacetylspermine as substrate, is described. The PAO was present in all human organs tested; it was highest in the liver, followed by the testis, kidney, spleen and small intestine. 相似文献
388.
The need for national HIV databases 总被引:1,自引:0,他引:1
Researchers and public health officials involved in surveying and forecasting the course of the HIV epidemic require complete and unfiltered information from many sources. Governments should respond by establishing national HIV databases. 相似文献
389.
Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin 总被引:138,自引:0,他引:138
T Hirano K Yasukawa H Harada T Taga Y Watanabe T Matsuda S Kashiwamura K Nakajima K Koyama A Iwamatsu 《Nature》1986,324(6092):73-76
When stimulated with antigen, B cells are influenced by T cells to proliferate and differentiate into antibody-forming cells. Since it was reported that soluble factors could replace certain functions of helper T cells in the antibody response, several different kinds of lymphokines and monokines have been reported in B-cell growth and differentiation. Among these, human B-cell differentiation factor (BCDF or BSF-2) has been shown to induce the final maturation of B cells into immunoglobulin-secreting cells. BSF-2 was purified to homogeneity and its partial NH2-terminal amino-acid sequence was determined. These studies indicated that BSF-2 is functionally and structurally unlike other known proteins. Here, we report the molecular cloning, structural analysis and functional expression of the cDNA encoding human BSF-2. The primary sequence of BSF-2 deduced from the cDNA reveals that BSF-2 is a novel interleukin consisting of 184 amino acids. 相似文献
390.
The T-cell subpopulations which initiate and mediate tissue allograft rejection remain controversial. In the present study we attempted to identify the phenotype and function of the T-cell subset(s) primarily responsible for the rejection of skin allografts differing at a single class I locus in the major histocompatibility complex (MHC). We found that the rejection rates by B6 mice (H-2b) of four different class I mutant (Kbm) skin allografts form a distinct hierarchy. This hierarchy correlates strikingly and uniquely with the relative precursor frequencies of Lyt2+ interleukin-2-secreting T-helper cells reactive against the various Kbm mutants. To investigate the role of Lyt2+ T cells in the rejection of class I-disparate skin allografts directly, H-2b nude mice were engrafted with Kbm skin allografts and then reconstituted with L3T4+ or Lyt2+ T-cell subpopulations from syngeneic H-2b mice. Lyt2+ T cells were observed to be both necessary and sufficient for the rejection of class I-disparate Kbm skin allografts, whereas L3T4+ T cells were neither necessary nor sufficient. These results identify the Lyt2+ interleukin-2-secreting T-cell subset as the critical cell type determining the rejection rate of class I-disparate Kbm skin allografts. 相似文献