全文获取类型
收费全文 | 11845篇 |
免费 | 24篇 |
国内免费 | 43篇 |
专业分类
系统科学 | 35篇 |
丛书文集 | 80篇 |
教育与普及 | 30篇 |
理论与方法论 | 42篇 |
现状及发展 | 5124篇 |
研究方法 | 565篇 |
综合类 | 5880篇 |
自然研究 | 156篇 |
出版年
2013年 | 96篇 |
2012年 | 191篇 |
2011年 | 330篇 |
2010年 | 85篇 |
2009年 | 59篇 |
2008年 | 190篇 |
2007年 | 222篇 |
2006年 | 203篇 |
2005年 | 224篇 |
2004年 | 208篇 |
2003年 | 208篇 |
2002年 | 198篇 |
2001年 | 379篇 |
2000年 | 364篇 |
1999年 | 263篇 |
1992年 | 232篇 |
1991年 | 180篇 |
1990年 | 204篇 |
1989年 | 190篇 |
1988年 | 201篇 |
1987年 | 206篇 |
1986年 | 160篇 |
1985年 | 248篇 |
1984年 | 170篇 |
1983年 | 149篇 |
1982年 | 166篇 |
1981年 | 135篇 |
1980年 | 170篇 |
1979年 | 385篇 |
1978年 | 291篇 |
1977年 | 287篇 |
1976年 | 249篇 |
1975年 | 287篇 |
1974年 | 309篇 |
1973年 | 308篇 |
1972年 | 344篇 |
1971年 | 344篇 |
1970年 | 428篇 |
1969年 | 361篇 |
1968年 | 381篇 |
1967年 | 351篇 |
1966年 | 319篇 |
1965年 | 203篇 |
1959年 | 107篇 |
1958年 | 204篇 |
1957年 | 137篇 |
1956年 | 122篇 |
1955年 | 105篇 |
1954年 | 81篇 |
1948年 | 83篇 |
排序方式: 共有10000条查询结果,搜索用时 921 毫秒
751.
Haemoglobin C protects against clinical Plasmodium falciparum malaria. 总被引:10,自引:0,他引:10
D Modiano G Luoni B S Sirima J Simporé F Verra A Konaté E Rastrelli A Olivieri C Calissano G M Paganotti L D'Urbano I Sanou A Sawadogo G Modiano M Coluzzi 《Nature》2001,414(6861):305-308
Haemoglobin C (HbC; beta6Glu --> Lys) is common in malarious areas of West Africa, especially in Burkina Faso. Conclusive evidence exists on the protective role against severe malaria of haemoglobin S (HbS; beta6Glu --> Val) heterozygosity, whereas conflicting results for the HbC trait have been reported and no epidemiological data exist on the possible role of the HbCC genotype. In vitro studies suggested that HbCC erythrocytes fail to support the growth of P. falciparum but HbC homozygotes with high P. falciparum parasitaemias have been observed. Here we show, in a large case-control study performed in Burkina Faso on 4,348 Mossi subjects, that HbC is associated with a 29% reduction in risk of clinical malaria in HbAC heterozygotes (P = 0.0008) and of 93% in HbCC homozygotes (P = 0.0011). These findings, together with the limited pathology of HbAC and HbCC compared to the severely disadvantaged HbSS and HbSC genotypes and the low betaS gene frequency in the geographic epicentre of betaC, support the hypothesis that, in the long term and in the absence of malaria control, HbC would replace HbS in central West Africa. 相似文献
752.
Thermoelectric materials are of interest for applications as heat pumps and power generators. The performance of thermoelectric devices is quantified by a figure of merit, ZT, where Z is a measure of a material's thermoelectric properties and T is the absolute temperature. A material with a figure of merit of around unity was first reported over four decades ago, but since then-despite investigation of various approaches-there has been only modest progress in finding materials with enhanced ZT values at room temperature. Here we report thin-film thermoelectric materials that demonstrate a significant enhancement in ZT at 300 K, compared to state-of-the-art bulk Bi2Te3 alloys. This amounts to a maximum observed factor of approximately 2.4 for our p-type Bi2Te3/Sb2Te3 superlattice devices. The enhancement is achieved by controlling the transport of phonons and electrons in the superlattices. Preliminary devices exhibit significant cooling (32 K at around room temperature) and the potential to pump a heat flux of up to 700 W cm-2; the localized cooling and heating occurs some 23,000 times faster than in bulk devices. We anticipate that the combination of performance, power density and speed achieved in these materials will lead to diverse technological applications: for example, in thermochemistry-on-a-chip, DNA microarrays, fibre-optic switches and microelectrothermal systems. 相似文献
753.
754.
Trans-complex formation by proteolipid channels in the terminal phase of membrane fusion 总被引:25,自引:0,他引:25
SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) and Rab-GTPases, together with their cofactors, mediate the attachment step in the membrane fusion of vesicles. But how bilayer mixing--the subsequent core process of fusion--is catalysed remains unclear. Ca2+/calmodulin controls this terminal process in many intracellular fusion events. Here we identify V0, the membrane-integral sector of the vacuolar H+-ATPase, as a target of calmodulin on yeast vacuoles. Between docking and bilayer fusion, V0 sectors from opposing membranes form complexes. V0 trans-complex formation occurs downstream from trans-SNARE pairing, and depends on both the Rab-GTPase Ypt7 and calmodulin. The maintenance of existing complexes and completion of fusion are independent of trans-SNARE pairs. Reconstituted proteolipids form sealed channels, which can expand to form aqueous pores in a Ca2+/calmodulin-dependent fashion. V0 trans-complexes may therefore form a continuous, proteolipid-lined channel at the fusion site. We propose that radial expansion of such a protein pore may be a mechanism for intracellular membrane fusion. 相似文献
755.
Pumping of nutrients to ocean surface waters by the action of propagating planetary waves 总被引:11,自引:0,他引:11
Primary productivity in the oceans is limited by the lack of nutrients in surface waters. These nutrients are mostly supplied from nutrient-rich subsurface waters through upwelling and vertical mixing, but in the ocean gyres these mechanisms do not fully account for the observed productivity. Recently, the upward pumping of nutrients, through the action of eddies, has been shown to account for the remainder of the primary productivity; however, these were regional studies which focused on mesoscale (100-km-scale) eddies. Here we analyse remotely sensed chlorophyll and sea-surface-height data collected over two years and show that 1,000-km-scale planetary waves, which propagate in a westward direction in the oceans, are associated with about 5 to 20% of the observed variability in chlorophyll concentration (after low-frequency and large-scale variations are removed from the data). Enhanced primary production is the likely explanation for this observation, and if that is the case, propagating disturbances introduce nutrients to surface waters on a global scale--similar to the nutrient pumping that occurs within distinct eddies. 相似文献
756.
Genome sequence of enterohaemorrhagic Escherichia coli O157:H7 总被引:31,自引:0,他引:31
Perna NT Plunkett G Burland V Mau B Glasner JD Rose DJ Mayhew GF Evans PS Gregor J Kirkpatrick HA Pósfai G Hackett J Klink S Boutin A Shao Y Miller L Grotbeck EJ Davis NW Lim A Dimalanta ET Potamousis KD Apodaca J Anantharaman TS Lin J Yen G Schwartz DC Welch RA Blattner FR 《Nature》2001,409(6819):529-533
The bacterium Escherichia coli O157:H7 is a worldwide threat to public health and has been implicated in many outbreaks of haemorrhagic colitis, some of which included fatalities caused by haemolytic uraemic syndrome. Close to 75,000 cases of O157:H7 infection are now estimated to occur annually in the United States. The severity of disease, the lack of effective treatment and the potential for large-scale outbreaks from contaminated food supplies have propelled intensive research on the pathogenesis and detection of E. coli O157:H7 (ref. 4). Here we have sequenced the genome of E. coli O157:H7 to identify candidate genes responsible for pathogenesis, to develop better methods of strain detection and to advance our understanding of the evolution of E. coli, through comparison with the genome of the non-pathogenic laboratory strain E. coli K-12 (ref. 5). We find that lateral gene transfer is far more extensive than previously anticipated. In fact, 1,387 new genes encoded in strain-specific clusters of diverse sizes were found in O157:H7. These include candidate virulence factors, alternative metabolic capacities, several prophages and other new functions--all of which could be targets for surveillance. 相似文献
757.
The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy 总被引:9,自引:0,他引:9
Eisenberg I Avidan N Potikha T Hochner H Chen M Olender T Barash M Shemesh M Sadeh M Grabov-Nardini G Shmilevich I Friedmann A Karpati G Bradley WG Baumbach L Lancet D Asher EB Beckmann JS Argov Z Mitrani-Rosenbaum S 《Nature genetics》2001,29(1):83-87
Hereditary inclusion body myopathy (HIBM; OMIM 600737) is a unique group of neuromuscular disorders characterized by adult onset, slowly progressive distal and proximal weakness and a typical muscle pathology including rimmed vacuoles and filamentous inclusions. The autosomal recessive form described in Jews of Persian descent is the HIBM prototype. This myopathy affects mainly leg muscles, but with an unusual distribution that spares the quadriceps. This particular pattern of weakness distribution, termed quadriceps-sparing myopathy (QSM), was later found in Jews originating from other Middle Eastern countries as well as in non-Jews. We previously localized the gene causing HIBM in Middle Eastern Jews on chromosome 9p12-13 (ref. 5) within a genomic interval of about 700 kb (ref. 6). Haplotype analysis around the HIBM gene region of 104 affected people from 47 Middle Eastern families indicates one unique ancestral founder chromosome in this community. By contrast, single non-Jewish families from India, Georgia (USA) and the Bahamas, with QSM and linkage to the same 9p12-13 region, show three distinct haplotypes. After excluding other potential candidate genes, we eventually identified mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) gene in the HIBM families: all patients from Middle Eastern descent shared a single homozygous missense mutation, whereas distinct compound heterozygotes were identified in affected individuals of families of other ethnic origins. Our findings indicate that GNE is the gene responsible for recessive HIBM. 相似文献
758.
Parkinson NJ Olsson CL Hallows JL McKee-Johnson J Keogh BP Noben-Trauth K Kujawa SG Tempel BL 《Nature genetics》2001,29(1):61-65
The autosomal recessive mouse mutation quivering (qv), which arose spontaneously in 1953, produces progressive ataxia with hind limb paralysis, deafness and tremor. Six additional spontaneous alleles, qvJ, qv2J, qv3J, qv4J, qvlnd and qvlnd2J, have been identified. Ear twitch responses (Preyer's reflex) to sound are absent in homozygous qv/qv mice, although cochlear morphology seems normal and cochlear potentials recorded at the round window are no different from those of control mice. However, responses from brainstem auditory nuclei show abnormal transmission of auditory information, indicating that, in contrast to the many known mutations causing deafness originating in the cochlea, deafness in qv is central in origin. Here we report that quivering mice carry loss-of-function mutations in the mouse beta-spectrin 4 gene (Spnb4) that cause alterations in ion channel localization in myelinated nerves; this provides a rationale for the auditory and motor neuropathies of these mice. 相似文献
759.
Hollopeter G Jantzen HM Vincent D Li G England L Ramakrishnan V Yang RB Nurden P Nurden A Julius D Conley PB 《Nature》2001,409(6817):202-207
Platelets have a crucial role in the maintenance of normal haemostasis, and perturbations of this system can lead to pathological thrombus formation and vascular occlusion, resulting in stroke, myocardial infarction and unstable angina. ADP released from damaged vessels and red blood cells induces platelet aggregation through activation of the integrin GPIIb-IIIa and subsequent binding of fibrinogen. ADP is also secreted from platelets on activation, providing positive feedback that potentiates the actions of many platelet activators. ADP mediates platelet aggregation through its action on two G-protein-coupled receptor subtypes. The P2Y1 receptor couples to Gq and mobilizes intracellular calcium ions to mediate platelet shape change and aggregation. The second ADP receptor required for aggregation (variously called P2Y(ADP), P2Y(AC), P2Ycyc or P2T(AC)) is coupled to the inhibition of adenylyl cyclase through Gi. The molecular identity of the Gi-linked receptor is still elusive, even though it is the target of efficacious antithrombotic agents, such as ticlopidine and clopidogrel and AR-C66096 (ref. 9). Here we describe the cloning of this receptor, designated P2Y12, and provide evidence that a patient with a bleeding disorder has a defect in this gene. Cloning of the P2Y12 receptor should facilitate the development of better antiplatelet agents to treat cardiovascular diseases. 相似文献
760.
Except in regions of recent crustal extension, the dominant origin of carbon dioxide in fluids in sedimentary basins has been assumed to be from crustal organic matter or mineral reactions. Here we show, by contrast, that Rayleigh fractionation caused by partial degassing of a magma body can explain the CO2/3He ratios and delta13C(CO2) values observed in CO2-rich natural gases in the west Texas Val Verde basin and also the mantle 3He/22Ne ratios observed in other basin systems. Regional changes in CO2/3He and CO2/CH4 ratios can be explained if the CO2 input pre-dates methane generation in the basin, which occurred about 280 Myr ago. Uplift to the north of the Val Verde basin between 310 and 280 Myr ago appears to be the only tectonic event with appropriate timing and location to be the source of the magmatic CO2. Our identification of magmatic CO2 in a foreland basin indicates that the origin of CO2 in other mid-continent basin systems should be re-evaluated. Also, the inferred closed-system preservation of natural gas in a trapping structure for approximately 300 Myr is far longer than the residence time predicted by diffusion models. 相似文献