全文获取类型
收费全文 | 15144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 | 73篇 |
现状及发展 | 6185篇 |
研究方法 | 787篇 |
综合类 | 7613篇 |
自然研究 | 285篇 |
出版年
2013年 | 105篇 |
2012年 | 264篇 |
2011年 | 544篇 |
2010年 | 106篇 |
2008年 | 322篇 |
2007年 | 304篇 |
2006年 | 321篇 |
2005年 | 329篇 |
2004年 | 319篇 |
2003年 | 280篇 |
2002年 | 260篇 |
2001年 | 458篇 |
2000年 | 442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 | 293篇 |
1984年 | 229篇 |
1983年 | 158篇 |
1982年 | 167篇 |
1981年 | 152篇 |
1980年 | 182篇 |
1979年 | 418篇 |
1978年 | 309篇 |
1977年 | 307篇 |
1976年 | 289篇 |
1975年 | 323篇 |
1974年 | 387篇 |
1973年 | 365篇 |
1972年 | 379篇 |
1971年 | 434篇 |
1970年 | 550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 15 毫秒
991.
YidC mediates membrane protein insertion in bacteria 总被引:13,自引:0,他引:13
Samuelson JC Chen M Jiang F Möller I Wiedmann M Kuhn A Phillips GJ Dalbey RE 《Nature》2000,406(6796):637-641
The basic machinery for the translocation of proteins into or across membranes is remarkably conserved from Escherichia coli to humans. In eukaryotes, proteins are inserted into the endoplasmic reticulum using the signal recognition particle (SRP) and the SRP receptor, as well as the integral membrane Sec61 trimeric complex (composed of alpha, beta and gamma subunits). In bacteria, most proteins are inserted by a related pathway that includes the SRP homologue Ffh, the SRP receptor FtsY, and the SecYEG trimeric complex, where Y and E are related to the Sec61 alpha and gamma subunits, respectively. Proteins in bacteria that exhibit no dependence on the Sec translocase were previously thought to insert into the membrane directly without the aid of a protein machinery. Here we show that membrane insertion of two Sec-independent proteins requires YidC. YidC is essential for E. coli viability and homologues are present in mitochondria and chloroplasts. Depletion of YidC also interferes with insertion of Sec-dependent membrane proteins, but it has only a minor effect on the export of secretory proteins. These results provide evidence for an additional component of the translocation machinery that is specialized for the integration of membrane proteins. 相似文献
992.
Helix deformation is coupled to vectorial proton transport in the photocycle of bacteriorhodopsin 总被引:10,自引:0,他引:10
A wide variety of mechanisms are used to generate a proton-motive potential across cell membranes, a function lying at the heart of bioenergetics. Bacteriorhodopsin, the simplest known proton pump, provides a paradigm for understanding this process. Here we report, at 2.1 A resolution, the structural changes in bacteriorhodopsin immediately preceding the primary proton transfer event in its photocycle. The early structural rearrangements propagate from the protein's core towards the extracellular surface, disrupting the network of hydrogen-bonded water molecules that stabilizes helix C in the ground state. Concomitantly, a bend of this helix enables the negatively charged primary proton acceptor, Asp 85, to approach closer to the positively charged primary proton donor, the Schiff base. The primary proton transfer event would then neutralize these two groups, cancelling their electrostatic attraction and facilitating a relaxation of helix C to a less strained geometry. Reprotonation of the Schiff base by Asp 85 would thereby be impeded, ensuring vectorial proton transport. Structural rearrangements also occur near the protein's surface, aiding proton release to the extracellular medium. 相似文献
993.
DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae 总被引:23,自引:0,他引:23
Heidelberg JF Eisen JA Nelson WC Clayton RA Gwinn ML Dodson RJ Haft DH Hickey EK Peterson JD Umayam L Gill SR Nelson KE Read TD Tettelin H Richardson D Ermolaeva MD Vamathevan J Bass S Qin H Dragoi I Sellers P McDonald L Utterback T Fleishmann RD Nierman WC White O Salzberg SL Smith HO Colwell RR Mekalanos JJ Venter JC Fraser CM 《Nature》2000,406(6795):477-483
994.
A sphingosine-1-phosphate receptor regulates cell migration during vertebrate heart development 总被引:13,自引:0,他引:13
Coordinated cell migration is essential in many fundamental biological processes including embryonic development, organogenesis, wound healing and the immune response. During organogenesis, groups of cells are directed to specific locations within the embryo. Here we show that the zebrafish miles apart (mil) mutation specifically affects the migration of the heart precursors to the midline. We found that mutant cells transplanted into a wild-type embryo migrate normally and that wild-type cells in a mutant embryo fail to migrate, suggesting that mil may be involved in generating an environment permissive for migration. We isolated mil by positional cloning and show that it encodes a member of the lysosphingolipid G-protein-coupled receptor family. We also show that sphingosine-1-phosphate is a ligand for Mil, and that it activates several downstream signalling events that are not activated by the mutant alleles. These data reveal a new role for lysosphingolipids in regulating cell migration during vertebrate development and provide the first molecular clues into the fusion of the bilateral heart primordia during organogenesis of the heart. 相似文献
995.
Luo Y Frey EA Pfuetzner RA Creagh AL Knoechel DG Haynes CA Finlay BB Strynadka NC 《Nature》2000,405(6790):1073-1077
Intimin and its translocated intimin receptor (Tir) are bacterial proteins that mediate adhesion between mammalian cells and attaching and effacing (A/E) pathogens. Enteropathogenic Escherichia coli (EPEC) causes significant paediatric morbidity and mortality world-wide. A related A/E pathogen, enterohaemorrhagic E. coli (EHEC; O157:H7) is one of the most important food-borne pathogens in North America, Europe and Japan. A unique and essential feature of A/E bacterial pathogens is the formation of actin-rich pedestals beneath the intimately adherent bacteria and localized destruction of the intestinal brush border. The bacterial outer membrane adhesin, intimin, is necessary for the production of the A/E lesion and diarrhoea. The A/E bacteria translocate their own receptor for intimin, Tir, into the membrane of mammalian cells using the type III secretion system. The translocated Tir triggers additional host signalling events and actin nucleation, which are essential for lesion formation. Here we describe the the crystal structures of an EPEC intimin carboxy-terminal fragment alone and in complex with the EPEC Tir intimin-binding domain, giving insight into the molecular mechanisms of adhesion of A/E pathogens. 相似文献
996.
Detection of preinvasive cancer cells 总被引:12,自引:0,他引:12
997.
Transformation from temporal to rate coding in a somatosensory thalamocortical pathway 总被引:20,自引:0,他引:20
The anatomical connections from the whiskers to the rodent somatosensory (barrel) cortex form two parallel (lemniscal and paralemniscal) pathways. It is unclear whether the paralemniscal pathway is directly involved in tactile processing, because paralemniscal neuronal responses show poor spatial resolution, labile latencies and strong dependence on cortical feedback. Here we show that the paralemniscal system can transform temporally encoded vibrissal information into a rate code. We recorded the representations of the frequency of whisker movement along the two pathways in anaesthetized rats. In response to varying stimulus frequencies, the lemniscal neurons exhibited amplitude modulations and constant latencies. In contrast, paralemniscal neurons in both thalamus and cortex coded the input frequency as changes in latency. Because the onset latencies increased and the offset latencies remained constant, the latency increments were translated into a rate code: increasing onset latencies led to lower spike counts. A thalamocortical loop that includes cortical oscillations and thalamic gating can account for these results. Thus, variable latencies and effective cortical feedback in the paralemniscal system can serve the processing of temporal sensory cues, such as those that encode object location during whisking. In contrast, fixed time locking in the lemniscal system is crucial for reliable spatial processing. 相似文献
998.
Identification of genes that modify ataxin-1-induced neurodegeneration 总被引:55,自引:0,他引:55
999.
The mammalian sodium channel BNC1 is required for normal touch sensation 总被引:27,自引:0,他引:27
Price MP Lewin GR McIlwrath SL Cheng C Xie J Heppenstall PA Stucky CL Mannsfeldt AG Brennan TJ Drummond HA Qiao J Benson CJ Tarr DE Hrstka RF Yang B Williamson RA Welsh MJ 《Nature》2000,407(6807):1007-1011
Of the vertebrate senses, touch is the least understood at the molecular level The ion channels that form the core of the mechanosensory complex and confer touch sensitivity remain unknown. However, the similarity of the brain sodium channel 1 (BNC1) to nematode proteins involved in mechanotransduction indicated that it might be a part of such a mechanosensor. Here we show that disrupting the mouse BNC1 gene markedly reduces the sensitivity of a specific component of mechanosensation: low-threshold rapidly adapting mechanoreceptors. In rodent hairy skin these mechanoreceptors are excited by hair movement. Consistent with this function, we found BNC1 in the lanceolate nerve endings that lie adjacent to and surround the hair follicle. Although BNC1 has been proposed to have a role in pH sensing, the acid-evoked current in cultured sensory neurons and the response of acid-stimulated nociceptors were normal in BNC1 null mice. These data identify the BNC1 channel as essential for the normal detection of light touch and indicate that BNC1 may be a central component of a mechanosensory complex. 相似文献
1000.
Microorganisms have flourished in the oceans since at least 3.8 billion years (3.8 Gyr) ago, but it is not at present clear when they first colonized the land. Organic matter in some Au/U-rich conglomerates and ancient soils of 2.3-2.7 Gyr age has been suggested as remnants of terrestrial organisms. Some 2.7-Gyr-old stromatolites have also been suggested as structures created by terrestrial organisms. However, it has been disputed whether this organic matter is indigenous or exogenic, and whether these stromatolites formed in marine or fresh water. Consequently, the oldest undisputed remnants of terrestrial organisms are currently the 1.2-Gyr-old microfossils from Arizona, USA. Unusually carbonaceous ancient soils--palaeosols--have been found in the Mpumalanga Province (Eastern Transvaal) of South Africa. Here we report the occurrences, elemental ratios (C, H, N, P) and isotopic compositions of this organic matter and its host rocks. These data show that the organic matter very probably represents remnants of microbial mats that developed on the soil surface between 2.6 and 2.7 Gyr ago. This places the development of terrestrial biomass more than 1.4 billion years earlier than previously reported. 相似文献