全文获取类型
收费全文 | 17321篇 |
免费 | 25篇 |
国内免费 | 67篇 |
专业分类
系统科学 | 126篇 |
丛书文集 | 288篇 |
教育与普及 | 43篇 |
理论与方法论 | 63篇 |
现状及发展 | 7414篇 |
研究方法 | 914篇 |
综合类 | 8302篇 |
自然研究 | 263篇 |
出版年
2013年 | 113篇 |
2012年 | 304篇 |
2011年 | 568篇 |
2010年 | 104篇 |
2009年 | 99篇 |
2008年 | 316篇 |
2007年 | 360篇 |
2006年 | 378篇 |
2005年 | 377篇 |
2004年 | 379篇 |
2003年 | 324篇 |
2002年 | 321篇 |
2001年 | 610篇 |
2000年 | 572篇 |
1999年 | 389篇 |
1992年 | 328篇 |
1991年 | 264篇 |
1990年 | 279篇 |
1989年 | 253篇 |
1988年 | 235篇 |
1987年 | 280篇 |
1986年 | 291篇 |
1985年 | 319篇 |
1984年 | 280篇 |
1983年 | 222篇 |
1982年 | 183篇 |
1981年 | 195篇 |
1980年 | 250篇 |
1979年 | 566篇 |
1978年 | 434篇 |
1977年 | 425篇 |
1976年 | 314篇 |
1975年 | 349篇 |
1974年 | 517篇 |
1973年 | 437篇 |
1972年 | 428篇 |
1971年 | 519篇 |
1970年 | 688篇 |
1969年 | 484篇 |
1968年 | 400篇 |
1967年 | 488篇 |
1966年 | 398篇 |
1965年 | 282篇 |
1959年 | 162篇 |
1958年 | 268篇 |
1957年 | 207篇 |
1956年 | 180篇 |
1955年 | 144篇 |
1954年 | 150篇 |
1948年 | 126篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
881.
Clustering of neurotransmitter receptors in the postsynaptic membrane is critical for efficient synaptic transmission. During
neuromuscular synaptogenesis, clustering of acetylcholine receptors (AChRs) is an early sign of postsynaptic differentiation.
Recent studies have revealed that the earliest AChR clusters can form in the muscle independent of motorneurons. Neurally
released agrin, acting through the muscle-specific kinase MuSK and rapsyn, then causes further clustering and localization
of clusters underneath the nerve terminal. AChRs themselves are required for agrin-induced clustering of several postsynaptic
proteins, most notably rapsyn. Once formed, AChR clusters are stabilized by several tyrosine kinases and by components of
the dystrophin/utrophin glycoprotein complex, some of which also direct postnatal synaptic maturation such as formation of
postjunctional folds. This review summarizes these recent results about AChR clustering, which indicate that early clustering
can occur in the absence of nerves, that AChRs play an active role in the clustering process and that partly different mechanisms
direct formation versus stabilization of AChR clusters.
Received 10 April 2002; received after revision 4 June 2002; accepted 10 June 2002 相似文献
882.
A polymorphic microsatellite that mediates induction of PIG3 by p53 总被引:16,自引:0,他引:16
883.
Harroch S Furtado GC Brueck W Rosenbluth J Lafaille J Chao M Buxbaum JD Schlessinger J 《Nature genetics》2002,32(3):411-414
Several lines of evidence suggest that tyrosine phosphorylation is a key element in myelin formation, differentiation of oligodendrocytes and Schwann cells, and recovery from demyelinating lesions. Multiple sclerosis is a demyelinating disease of the human central nervous system, and studies of experimental demyelination indicate that remyelination in vivo requires the local generation, migration or maturation of new oligodendrocytes, or some combination of these. Failure of remyelination in multiple sclerosis could result from the failure of any of these processes or from the death of oligodendrocytes. Ptprz encodes protein tyrosine phosphatase receptor type Z (Ptpz, also designated Rptpbeta), which is expressed primarily in the nervous system but also in oligodendrocytes, astrocytes and neurons. Here we examine the susceptibility of mice deficient in Ptprz to experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. We observe that mice deficient in Ptprz show impaired recovery from EAE induced by myelin oligodendrocyte glycoprotein (MOG) peptide. This sustained paralysis is associated with increased apoptosis of mature oligodendrocytes in the spinal cords of mutant mice at the peak of inflammation. We further demonstrate that expression of PTPRZ1, the human homolog of Ptprz, is induced in multiple sclerosis lesions and that the gene is specifically expressed in remyelinating oligodendrocytes in these lesions. These results support a role for Ptprz in oligodendrocyte survival and in recovery from demyelinating disease. 相似文献
884.
Kapfhamer D Valladares O Sun Y Nolan PM Rux JJ Arnold SE Veasey SC Bućan M 《Nature genetics》2002,32(2):290-295
Rab3a is the most abundant Rab (ras-associated binding) protein in the brain and has a regulatory role in synaptic vesicle trafficking. Mice with a targeted loss-of-function mutation in Rab3a have defects in Ca(2+)-dependent synaptic transmission: the number of vesicles released in response to an action potential is greater than in wildtype mice, resulting in greater synaptic depression and the abolishment of CA3 mossy-fiber long term potentiation. The effect of these changes on behavior is unknown. In a screen for mouse mutants with abnormal rest-activity and sleep patterns, we identified a semidominant mutation, called earlybird, that shortens the circadian period of locomotor activity. Sequence analysis of Rab3a identified a point mutation in the conserved amino acid (Asp77Gly) within the GTP-binding domain of this protein in earlybird mutants, resulting in significantly reduced levels of Rab3a protein. Phenotypic assessment of earlybird mice and a null allele of Rab3a revealed anomalies in circadian period and sleep homeostasis, providing evidence that Rab3a-mediated synaptic transmission is involved in these behaviors. 相似文献
885.
886.
Walder RY Landau D Meyer P Shalev H Tsolia M Borochowitz Z Boettger MB Beck GE Englehardt RK Carmi R Sheffield VC 《Nature genetics》2002,31(2):171-174
Familial hypomagnesemia with secondary hypocalcemia (OMIM 602014) is an autosomal recessive disease that results in electrolyte abnormalities shortly after birth. Affected individuals show severe hypomagnesemia and hypocalcemia, which lead to seizures and tetany. The disorder has been thought to be caused by a defect in the intestinal absorption of magnesium, rather than by abnormal renal loss of magnesium. Restoring the concentrations of serum magnesium to normal values by high-dose magnesium supplementation can overcome the apparent defect in magnesium absorption and in serum concentrations of calcium. Life-long magnesium supplementation is required to overcome the defect in magnesium handling by these individuals. We previously mapped the gene locus to chromosome 9q in three large inbred kindreds from Israel. Here we report that mutation of TRPM6 causes hypomagnesemia with secondary hypocalcemia and show that individuals carrying mutations in this gene have abnormal renal magnesium excretion. 相似文献
887.
Crumbs, the Drosophila homologue of human CRB1/RP12, is essential for photoreceptor morphogenesis 总被引:3,自引:0,他引:3
The apical transmembrane protein Crumbs is a central regulator of epithelial apical-basal polarity in Drosophila. Loss-of-function mutations in the human homologue of Crumbs, CRB1 (RP12), cause recessive retinal dystrophies, including retinitis pigmentosa. Here we show that Crumbs and CRB1 localize to corresponding subdomains of the photoreceptor apical plasma membrane: the stalk of the Drosophila photoreceptor and the inner segment of mammalian photoreceptors. These subdomains support the morphogenesis and orientation of the photosensitive membrane organelles: rhabdomeres and outer segments, respectively. Drosophila Crumbs is required to maintain zonula adherens integrity during the rapid apical membrane expansion that builds the rhabdomere. Crumbs also regulates stalk development by stabilizing the membrane-associated spectrin cytoskeleton, a function mechanistically distinct from its role in epithelial apical-basal polarity. We propose that Crumbs is a central component of a molecular scaffold that controls zonula adherens assembly and defines the stalk as an apical membrane subdomain. Defects in such scaffolds may contribute to human CRB1-related retinal dystrophies. 相似文献
888.
Advanced materials and processing techniques are based largely on the generation and control of non-homogeneous microstructures, such as precipitates and grain boundaries. X-ray tomography can provide three-dimensional density and chemical distributions of such structures with submicrometre resolution; structural methods exist that give submicrometre resolution in two dimensions; and techniques are available for obtaining grain-centroid positions and grain-average strains in three dimensions. But non-destructive point-to-point three-dimensional structural probes have not hitherto been available for investigations at the critical mesoscopic length scales (tenths to hundreds of micrometres). As a result, investigations of three-dimensional mesoscale phenomena--such as grain growth, deformation, crumpling and strain-gradient effects--rely increasingly on computation and modelling without direct experimental input. Here we describe a three-dimensional X-ray microscopy technique that uses polychromatic synchrotron X-ray microbeams to probe local crystal structure, orientation and strain tensors with submicrometre spatial resolution. We demonstrate the utility of this approach with micrometre-resolution three-dimensional measurements of grain orientations and sizes in polycrystalline aluminium, and with micrometre depth-resolved measurements of elastic strain tensors in cylindrically bent silicon. This technique is applicable to single-crystal, polycrystalline, composite and functionally graded materials. 相似文献
889.
Homogeneous organometallic catalysts and many enzymes activate reactants through coordination to metal atoms; that is, the reactants are turned into ligands and their reactivity controlled through other ligands in the metal's coordination sphere. In the case of supported metal clusters, catalytic performance is influenced by the support and by adsorbed reactants, intermediates or products. The adsorbates are usually treated as ligands, whereas the influence of the supports is usually ascribed to electronic interactions, even though metal clusters supported on oxides and zeolites form chemical bonds to support oxygen atoms. Here we report direct observations of the structure of supported metal clusters consisting of four iridium atoms, and the identification of hydrocarbon ligands bound to them during propene hydrogenation. We find that propene and molecular hydrogen form propylidyne and hydride ligands, respectively, whereas simultaneous exposure of the reactants to the supported iridium cluster yields ligands that are reactive intermediates during the catalytic propane-formation reaction. These intermediates weaken the bonding within the tetrahedral iridium cluster and the interactions between the cluster and the support, while replacement of the MgO support with gamma-Al2O3 boosts the catalytic activity tenfold, by affecting the bonding between the reactant-derived ligands and the cluster and therefore also the abundance of individual ligands. This interplay between the support and the reactant-derived ligands, whereby each influences the interaction of the metal cluster with the other, shows that the catalytic properties of supported metal catalysts can be tuned by careful choice of their supports. 相似文献
890.
Kurth WS Gurnett DA Hospodarsky GB Farrell WM Roux A Dougherty MK Joy SP Kivelson MG Walker RJ Crary FJ Alexander CJ 《Nature》2002,415(6875):991-994
Limited single-spacecraft observations of Jupiter's magnetopause have been used to infer that the boundary moves inward or outward in response to variations in the dynamic pressure of the solar wind. At Earth, multiple-spacecraft observations have been implemented to understand the physics of how this motion occurs, because they can provide a snapshot of a transient event in progress. Here we present a set of nearly simultaneous two-point measurements of the jovian magnetopause at a time when the jovian magnetopause was in a state of transition from a relatively larger to a relatively smaller size in response to an increase in solar-wind pressure. The response of Jupiter's magnetopause is very similar to that of the Earth, confirming that the understanding built on studies of the Earth's magnetosphere is valid. The data also reveal evidence for a well-developed boundary layer just inside the magnetopause. 相似文献