全文获取类型
收费全文 | 15161篇 |
免费 | 28篇 |
国内免费 | 47篇 |
专业分类
系统科学 | 63篇 |
丛书文集 | 181篇 |
教育与普及 | 32篇 |
理论与方法论 | 74篇 |
现状及发展 | 6190篇 |
研究方法 | 788篇 |
综合类 | 7622篇 |
自然研究 | 286篇 |
出版年
2013年 | 105篇 |
2012年 | 265篇 |
2011年 | 547篇 |
2010年 | 105篇 |
2008年 | 324篇 |
2007年 | 304篇 |
2006年 | 322篇 |
2005年 | 331篇 |
2004年 | 319篇 |
2003年 | 282篇 |
2002年 | 260篇 |
2001年 | 459篇 |
2000年 | 446篇 |
1999年 | 311篇 |
1992年 | 267篇 |
1991年 | 197篇 |
1990年 | 224篇 |
1989年 | 219篇 |
1988年 | 223篇 |
1987年 | 218篇 |
1986年 | 205篇 |
1985年 | 294篇 |
1984年 | 229篇 |
1983年 | 158篇 |
1982年 | 167篇 |
1981年 | 153篇 |
1980年 | 181篇 |
1979年 | 418篇 |
1978年 | 309篇 |
1977年 | 307篇 |
1976年 | 289篇 |
1975年 | 323篇 |
1974年 | 386篇 |
1973年 | 365篇 |
1972年 | 379篇 |
1971年 | 434篇 |
1970年 | 552篇 |
1969年 | 462篇 |
1968年 | 469篇 |
1967年 | 431篇 |
1966年 | 383篇 |
1965年 | 285篇 |
1964年 | 87篇 |
1959年 | 169篇 |
1958年 | 297篇 |
1957年 | 199篇 |
1956年 | 185篇 |
1955年 | 150篇 |
1954年 | 185篇 |
1948年 | 138篇 |
排序方式: 共有10000条查询结果,搜索用时 109 毫秒
991.
Wehrli M Dougan ST Caldwell K O'Keefe L Schwartz S Vaizel-Ohayon D Schejter E Tomlinson A DiNardo S 《Nature》2000,407(6803):527-530
The Wnt family of secreted molecules functions in cell-fate determination and morphogenesis during development in both vertebrates and invertebrates (reviewed in ref. 1). Drosophila Wingless is a founding member of this family, and many components of its signal transduction cascade have been identified, including the Frizzled class of receptor. But the mechanism by which the Wingless signal is received and transduced across the membrane is not completely understood. Here we describe a gene that is necessary for all Wingless signalling events in Drosophila. We show that arrow gene function is essential in cells receiving Wingless input and that it acts upstream of Dishevelled. arrow encodes a single-pass transmembrane protein, indicating that it may be part of a receptor complex with Frizzled class proteins. Arrow is a low-density lipoprotein (LDL)-receptor-related protein (LRP), strikingly homologous to murine and human LRP5 and LRP6. Thus, our data suggests a new and conserved function for this LRP subfamily in Wingless/Wnt signal reception. 相似文献
992.
993.
Tat-specific cytotoxic T lymphocytes select for SIV escape variants during resolution of primary viraemia 总被引:55,自引:0,他引:55
Allen TM O'Connor DH Jing P Dzuris JL Mothé BR Vogel TU Dunphy E Liebl ME Emerson C Wilson N Kunstman KJ Wang X Allison DB Hughes AL Desrosiers RC Altman JD Wolinsky SM Sette A Watkins DI 《Nature》2000,407(6802):386-390
Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections are characterized by early peaks of viraemia that decline as strong cellular immune responses develop. Although it has been shown that virus-specific CD8-positive cytotoxic T lymphocytes (CTLs) exert selective pressure during HIV and SIV infection, the data have been controversial. Here we show that Tat-specific CD8-positive T-lymphocyte responses select for new viral escape variants during the acute phase of infection. We sequenced the entire virus immediately after the acute phase, and found that amino-acid replacements accumulated primarily in Tat CTL epitopes. This implies that Tat-specific CTLs may be significantly involved in controlling wild-type virus replication, and suggests that responses against viral proteins that are expressed early during the viral life cycle might be attractive targets for HIV vaccine development. 相似文献
994.
995.
Subduction and collision processes in the Central Andes constrained by converted seismic phases 总被引:5,自引:0,他引:5
Yuan X Sobolev SV Kind R Oncken O Bock G Asch G Schurr B Graeber F Rudloff A Hanka W Wylegalla K Tibi R Haberland C Rietbrock A Giese P Wigger P Röwer P Zandt G Beck S Wallace T Pardo M Comte D 《Nature》2000,408(6815):958-961
The Central Andes are the Earth's highest mountain belt formed by ocean-continent collision. Most of this uplift is thought to have occurred in the past 20 Myr, owing mainly to thickening of the continental crust, dominated by tectonic shortening. Here we use P-to-S (compressional-to-shear) converted teleseismic waves observed on several temporary networks in the Central Andes to image the deep structure associated with these tectonic processes. We find that the Moho (the Mohorovici? discontinuity--generally thought to separate crust from mantle) ranges from a depth of 75 km under the Altiplano plateau to 50 km beneath the 4-km-high Puna plateau. This relatively thin crust below such a high-elevation region indicates that thinning of the lithospheric mantle may have contributed to the uplift of the Puna plateau. We have also imaged the subducted crust of the Nazca oceanic plate down to 120 km depth, where it becomes invisible to converted teleseismic waves, probably owing to completion of the gabbro-eclogite transformation; this is direct evidence for the presence of kinetically delayed metamorphic reactions in subducting plates. Most of the intermediate-depth seismicity in the subducting plate stops at 120 km depth as well, suggesting a relation with this transformation. We see an intracrustal low-velocity zone, 10-20 km thick, below the entire Altiplano and Puna plateaux, which we interpret as a zone of continuing metamorphism and partial melting that decouples upper-crustal imbrication from lower-crustal thickening. 相似文献
996.
A beta peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease 总被引:50,自引:0,他引:50
Janus C Pearson J McLaurin J Mathews PM Jiang Y Schmidt SD Chishti MA Horne P Heslin D French J Mount HT Nixon RA Mercken M Bergeron C Fraser PE St George-Hyslop P Westaway D 《Nature》2000,408(6815):979-982
Much evidence indicates that abnormal processing and extracellular deposition of amyloid-beta peptide (A beta), a proteolytic derivative of the beta-amyloid precursor protein (betaAPP), is central to the pathogenesis of Alzheimer's disease (reviewed in ref. 1). In the PDAPP transgenic mouse model of Alzheimer's disease, immunization with A beta causes a marked reduction in burden of the brain amyloid. Evidence that A beta immunization also reduces cognitive dysfunction in murine models of Alzheimer's disease would support the hypothesis that abnormal A beta processing is essential to the pathogenesis of Alzheimer's disease, and would encourage the development of other strategies directed at the 'amyloid cascade'. Here we show that A beta immunization reduces both deposition of cerebral fibrillar A beta and cognitive dysfunction in the TgCRND8 murine model of Alzheimer's disease without, however, altering total levels of A beta in the brain. This implies that either a approximately 50% reduction in dense-cored A beta plaques is sufficient to affect cognition, or that vaccination may modulate the activity/abundance of a small subpopulation of especially toxic A beta species. 相似文献
997.
998.
Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain 总被引:34,自引:0,他引:34
Liu Z Sun C Olejniczak ET Meadows RP Betz SF Oost T Herrmann J Wu JC Fesik SW 《Nature》2000,408(6815):1004-1008
The inhibitor-of-apoptosis proteins (IAPs) regulate programmed cell death by inhibiting members of the caspase family of enzymes. Recently, a mammalian protein called Smac (also named DIABLO) was identified that binds to the IAPs and promotes caspase activation. Although undefined in the X-ray structure, the amino-terminal residues of Smac are critical for its function. To understand the structural basis for molecular recognition between Smac and the IAPs, we determined the solution structure of the BIR3 domain of X-linked IAP (XIAP) complexed with a functionally active nine-residue peptide derived from the N terminus of Smac. The peptide binds across the third beta-strand of the BIR3 domain in an extended conformation with only the first four residues contacting the protein. The complex is stabilized by four intermolecular hydrogen bonds, an electrostatic interaction involving the N terminus of the peptide, and several hydrophobic interactions. This structural information, along with the binding data from BIR3 and Smac peptide mutants reported here, should aid in the design of small molecules that may be used for the treatment of cancers that overexpress IAPs. 相似文献
999.
The type III inositol 1,4,5-trisphosphate receptor (InsP3R) is an important intracellular calcium (Ca2+) release channel in the pancreatic beta cell. Pancreatic beta cells secrete insulin following a characteristic change in membrane potential that leads to an increase in cytoplasmic Ca2+. Both extracellular Ca2+ and Ca2+ mobilized from InsP3-sensitive stores contribute to this increase. RIN-m5F cells, an insulin-secreting beta cell line, preferentially express the type III InsP3R. These cells have been useful in determining the regulatory properties of the type III InsP3R and the role of this isoform in an intact cell. The type III InsP3R is ideal for signal initiation because high cytoplasmic Ca2+ does not inhibit its activity. Altered insulin secretion, the result of changes in Ca2+ handling by the beta cell, has significant clinical consequences. 相似文献
1000.