全文获取类型
收费全文 | 16803篇 |
免费 | 35篇 |
国内免费 | 37篇 |
专业分类
系统科学 | 71篇 |
丛书文集 | 263篇 |
教育与普及 | 30篇 |
理论与方法论 | 71篇 |
现状及发展 | 7996篇 |
研究方法 | 693篇 |
综合类 | 7590篇 |
自然研究 | 161篇 |
出版年
2013年 | 76篇 |
2012年 | 185篇 |
2011年 | 364篇 |
2008年 | 222篇 |
2007年 | 241篇 |
2006年 | 279篇 |
2005年 | 270篇 |
2004年 | 376篇 |
2003年 | 254篇 |
2002年 | 254篇 |
2001年 | 479篇 |
2000年 | 442篇 |
1999年 | 324篇 |
1994年 | 74篇 |
1992年 | 286篇 |
1991年 | 225篇 |
1990年 | 238篇 |
1989年 | 235篇 |
1988年 | 202篇 |
1987年 | 234篇 |
1986年 | 278篇 |
1985年 | 335篇 |
1984年 | 230篇 |
1983年 | 226篇 |
1982年 | 205篇 |
1981年 | 217篇 |
1980年 | 224篇 |
1979年 | 563篇 |
1978年 | 475篇 |
1977年 | 437篇 |
1976年 | 341篇 |
1975年 | 404篇 |
1974年 | 564篇 |
1973年 | 452篇 |
1972年 | 472篇 |
1971年 | 553篇 |
1970年 | 696篇 |
1969年 | 538篇 |
1968年 | 539篇 |
1967年 | 536篇 |
1966年 | 430篇 |
1965年 | 371篇 |
1964年 | 121篇 |
1959年 | 193篇 |
1958年 | 330篇 |
1957年 | 247篇 |
1956年 | 190篇 |
1955年 | 192篇 |
1954年 | 190篇 |
1948年 | 127篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
921.
Juxtaposed regions of extensive and minimal linkage disequilibrium in human Xq25 and Xq28 总被引:20,自引:0,他引:20
Taillon-Miller P Bauer-Sardiña I Saccone NL Putzel J Laitinen T Cao A Kere J Pilia G Rice JP Kwok PY 《Nature genetics》2000,25(3):324-328
Linkage disequilibrium (LD), or the non-random association of alleles, is poorly understood in the human genome. Population genetic theory suggests that LD is determined by the age of the markers, population history, recombination rate, selection and genetic drift. Despite the uncertainties in determining the relative contributions of these factors, some groups have argued that LD is a simple function of distance between markers. Disease-gene mapping studies and a simulation study gave differing predictions on the degree of LD in isolated and general populations. In view of the discrepancies between theory and experimental observations, we constructed a high-density SNP map of the Xq25-Xq28 region and analysed the male genotypes and haplotypes across this region for LD in three populations. The populations included an outbred European sample (CEPH males) and isolated population samples from Finland and Sardinia. We found two extended regions of strong LD bracketed by regions with no evidence for LD in all three samples. Haplotype analysis showed a paucity of haplotypes in regions of strong LD. Our results suggest that, in this region of the X chromosome, LD is not a monotonic function of the distance between markers, but is more a property of the particular location in the human genome. 相似文献
922.
Single-molecule studies of the effect of template tension on T7 DNA polymerase activity 总被引:8,自引:0,他引:8
T7 DNA polymerase catalyses DNA replication in vitro at rates of more than 100 bases per second and has a 3'-->5' exonuclease (nucleotide removing) activity at a separate active site. This enzyme possesses a 'right hand' shape which is common to most polymerases with fingers, palm and thumb domains. The rate-limiting step for replication is thought to involve a conformational change between an 'open fingers' state in which the active site samples nucleotides, and a 'closed' state in which nucleotide incorporation occurs. DNA polymerase must function as a molecular motor converting chemical energy into mechanical force as it moves over the template. Here we show, using a single-molecule assay based on the differential elasticity of single-stranded and double-stranded DNA, that mechanical force is generated during the rate-limiting step and that the motor can work against a maximum template tension of approximately 34 pN. Estimates of the mechanical and entropic work done by the enzyme show that T7 DNA polymerase organizes two template bases in the polymerization site during each catalytic cycle. We also find a force-induced 100-fold increase in exonucleolysis above 40 pN. 相似文献
923.
A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae 总被引:85,自引:0,他引:85
Uetz P Giot L Cagney G Mansfield TA Judson RS Knight JR Lockshon D Narayan V Srinivasan M Pochart P Qureshi-Emili A Li Y Godwin B Conover D Kalbfleisch T Vijayadamodar G Yang M Johnston M Fields S Rothberg JM 《Nature》2000,403(6770):623-627
Two large-scale yeast two-hybrid screens were undertaken to identify protein-protein interactions between full-length open reading frames predicted from the Saccharomyces cerevisiae genome sequence. In one approach, we constructed a protein array of about 6,000 yeast transformants, with each transformant expressing one of the open reading frames as a fusion to an activation domain. This array was screened by a simple and automated procedure for 192 yeast proteins, with positive responses identified by their positions in the array. In a second approach, we pooled cells expressing one of about 6,000 activation domain fusions to generate a library. We used a high-throughput screening procedure to screen nearly all of the 6,000 predicted yeast proteins, expressed as Gal4 DNA-binding domain fusion proteins, against the library, and characterized positives by sequence analysis. These approaches resulted in the detection of 957 putative interactions involving 1,004 S. cerevisiae proteins. These data reveal interactions that place functionally unclassified proteins in a biological context, interactions between proteins involved in the same biological function, and interactions that link biological functions together into larger cellular processes. The results of these screens are shown here. 相似文献
924.
Myoglobin-like aerotaxis transducers in Archaea and Bacteria 总被引:14,自引:0,他引:14
Haem-containing proteins such as haemoglobin and myoglobin play an essential role in oxygen transport and storage. Comparison of the amino-acid sequences of globins from Bacteria and Eukarya suggests that they share an early common ancestor, even though the proteins perform different functions in these two kingdoms. Until now, no members of the globin family have been found in the third kingdom, Archaea. Recent studies of biological signalling in the Bacteria and Eukarya have revealed a new class of haem-containing proteins that serve as sensors. Until now, no haem-based sensor has been described in the Archaea. Here we report the first myoglobin-like, haem-containing protein in the Archaea, and the first haem-based aerotactic transducer in the Bacteria (termed HemAT-Hs for the archaeon Halobacterium salinarum, and HemAT-Bs for Bacillus subtilis). These proteins exhibit spectral properties similar to those of myoglobin and trigger aerotactic responses. 相似文献
925.
Inhibitor of neurite outgrowth in humans 总被引:82,自引:0,他引:82
Prinjha R Moore SE Vinson M Blake S Morrow R Christie G Michalovich D Simmons DL Walsh FS 《Nature》2000,403(6768):383-384
926.
NO is necessary and sufficient for egg activation at fertilization 总被引:14,自引:0,他引:14
Kuo RC Baxter GT Thompson SH Stricker SA Patton C Bonaventura J Epel D 《Nature》2000,406(6796):633-636
The early steps that lead to the rise in calcium and egg activation at fertilization are unknown but of great interest--particularly with the advent of in vitro fertilization techniques for treating male infertility and whole-animal cloning by nuclear transfer. This calcium rise is required for egg activation and the subsequent events of development in eggs of all species. Injection of intact sperm or sperm extracts can activate eggs, suggesting that sperm-derived factors may be involved. Here we show that nitric oxide synthase is present at high concentration and active in sperm after activation by the acrosome reaction. An increase in nitrosation within eggs is evident seconds after insemination and precedes the calcium pulse of fertilization. Microinjection of nitric oxide donors or recombinant nitric oxide synthase recapitulates events of egg activation, whereas prior injection of oxyhaemoglobin, a physiological nitric oxide scavenger, prevents egg activation after fertilization. We conclude that nitric oxide synthase and nitric-oxide-related bioactivity satisfy the primary criteria of an egg activator: they are present in an appropriate place, active at an appropriate time, and are necessary and sufficient for successful fertilization. 相似文献
927.
Quasi-planar nucleus structure in apoferritin crystallization 总被引:1,自引:0,他引:1
First-order phase transitions of matter, such as condensation and crystallization, proceed through the formation and subsequent growth of 'critical nuclei' of the new phase. The thermodynamics and kinetics of the formation of these critical nuclei depend on their structure, which is often assumed to be a compact, three-dimensional arrangement of the constituent molecules or atoms. Recent molecular dynamics simulations have predicted compact nucleus structures for matter made up of building blocks with a spherical interaction field, whereas strongly anisotropic, dipolar molecules may form nuclei consisting of single chains of molecules. Here we show, using direct atomic force microscopy observations, that the near-critical-size clusters formed during the crystallization of apoferritin, a quasi-spherical protein, and which are representative of the critical nucleus of this system, consist of planar arrays of one or two monomolecular layers that contain 5-10 rods of up to 7 molecules each. We find that these clusters contain between 20 and 50 molecules each, and that the arrangement of the constituent molecules is identical to that found in apoferritin crystals. We anticipate that similarly unexpected critical nucleus structures may be quite common, particularly with anisotropic molecules, suggesting that advanced nucleation theories should treat the critical nucleus structure as a variable. 相似文献
928.
Two yeast forkhead genes regulate the cell cycle and pseudohyphal growth 总被引:36,自引:0,他引:36
929.
930.
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