全文获取类型
收费全文 | 32302篇 |
免费 | 137篇 |
国内免费 | 276篇 |
专业分类
系统科学 | 630篇 |
丛书文集 | 791篇 |
教育与普及 | 105篇 |
理论与方法论 | 105篇 |
现状及发展 | 13140篇 |
研究方法 | 1213篇 |
综合类 | 16085篇 |
自然研究 | 646篇 |
出版年
2013年 | 327篇 |
2012年 | 620篇 |
2011年 | 1323篇 |
2010年 | 435篇 |
2009年 | 420篇 |
2008年 | 731篇 |
2007年 | 879篇 |
2006年 | 813篇 |
2005年 | 762篇 |
2004年 | 603篇 |
2003年 | 573篇 |
2002年 | 513篇 |
2001年 | 973篇 |
2000年 | 1012篇 |
1999年 | 636篇 |
1992年 | 532篇 |
1991年 | 445篇 |
1990年 | 484篇 |
1989年 | 449篇 |
1988年 | 428篇 |
1987年 | 451篇 |
1986年 | 423篇 |
1985年 | 535篇 |
1984年 | 430篇 |
1983年 | 345篇 |
1982年 | 337篇 |
1981年 | 366篇 |
1980年 | 420篇 |
1979年 | 946篇 |
1978年 | 733篇 |
1977年 | 769篇 |
1976年 | 573篇 |
1975年 | 618篇 |
1974年 | 934篇 |
1973年 | 785篇 |
1972年 | 725篇 |
1971年 | 869篇 |
1970年 | 1064篇 |
1969年 | 922篇 |
1968年 | 842篇 |
1967年 | 897篇 |
1966年 | 762篇 |
1965年 | 586篇 |
1964年 | 183篇 |
1959年 | 338篇 |
1958年 | 495篇 |
1957年 | 354篇 |
1956年 | 294篇 |
1955年 | 295篇 |
1954年 | 276篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
961.
Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production. 总被引:41,自引:0,他引:41
M Citron T Oltersdorf C Haass L McConlogue A Y Hung P Seubert C Vigo-Pelfrey I Lieberburg D J Selkoe 《Nature》1992,360(6405):672-674
Progressive cerebral deposition of the 39-43-amino-acid amyloid beta-protein (A beta) is an invariant feature of Alzheimer's disease which precedes symptoms of dementia by years or decades. The only specific molecular defects that cause Alzheimer's disease which have been identified so far are missense mutations in the gene encoding the beta-amyloid precursor protein (beta-APP) in certain families with an autosomal dominant form of the disease (familial Alzheimer's disease, or FAD). These mutations are located within or immediately flanking the A beta region of beta-APP, but the mechanism by which they cause the pathological phenotype of early and accelerated A beta deposition is unknown. Here we report that cultured cells which express a beta-APP complementary DNA bearing a double mutation (Lys to Asn at residue 595 plus Met to Leu at position 596) found in a Swedish FAD family produce approximately 6-8-fold more A beta than cells expressing normal beta-APP. The Met 596 to Leu mutation is principally responsible for the increase. These data establish a direct link between a FAD genotype and the clinicopathological phenotype. Further, they confirm the relevance of the continuous A beta production by cultured cells for elucidating the fundamental mechanism of Alzheimer's disease. 相似文献
962.
The thymus positively selects thymocytes that bear T-cell receptors which recognize antigen presented by self major histocompatibility complex (MHC) proteins. Positive selection is usually driven by MHC products on radiation-resistant cortical epithelial cells. It is unknown whether positive selection is mediated by all thymic epithelial cells or by some specialized subsets. Here we introduce an H-2b-expressing thymic epithelial cell line into the thymuses of lethally irradiated H-2k animals reconstituted with H-2b/k F1 BM or fetal liver cells. I-Ab-restricted T cells are found in these animals, demonstrating that selection occurs on the introduced epithelial cells. 相似文献
963.
964.
Mitochondria contain a complex machinery for the import of nuclear-encoded proteins. Receptor proteins exposed on the outer membrane surface are required for the specific binding of precursor proteins to mitochondria, either by binding of cytosolic signal recognition factors or by direct recognition of the precursor polypeptides. Subsequently, the precursors are inserted into the outer membrane at the general insertion site GIP (general insertion protein). Here we report the analysis of receptors and GIP by crosslinking of translocation intermediates and by coimmunoprecipitation. Surface-accumulated precursors were crosslinked to the receptors MOM19 and MOM72, suggesting a direct interaction of preproteins with surface receptors. We identified three novel mitochondrial outer membrane proteins, MOM7, MOM8, and MOM30 that, together with the previously identified MOM38, seem to form the GIP site and are present in the mitochondrial receptor complex. 相似文献
965.
Close linkage of glucokinase locus on chromosome 7p to early-onset non-insulin-dependent diabetes mellitus. 总被引:22,自引:0,他引:22
P Froguel M Vaxillaire F Sun G Velho H Zouali M O Butel S Lesage N Vionnet K Clément F Fougerousse 《Nature》1992,356(6365):162-164
Non-insulin-dependent diabetes mellitus (NIDDM) is a major health problem, affecting 5% of the world population. Genetic factors are important in NIDDM, but the mechanisms leading to glucose intolerance are unknown. Genetic linkage has been investigated in multigeneration families to localize, and ultimately identify, the gene(s) predisposing to NIDDM. Here we report linkage between the glucokinase locus on chromosome 7p and diabetes in 16 French families with maturity-onset diabetes of the young, a form of NIDDM characterized by monogenic autosomal dominant transmission and early age of onset. Statistical evidence of genetic heterogeneity was significant, with an estimated 45-95% of the 16 families showing linkage to glucokinase. Because glucokinase is a key enzyme of blood glucose homeostasis, these results are evidence that a gene involved in glucose metabolism could be implicated in the pathogenesis of NIDDM. 相似文献
966.
We report here the discovery of a Miocene hominoid from Berg Aukas, Namibia, the first known from the African continent south of equatorial East Africa. This represents a major range extension of Miocene Hominoidea in Africa to latitude 20 degrees S. The holotype, a right mandibular corpus preserving the crowns of the P4-M3, partial crown and root of the P3, partial root of the canine, alveoli for all four incisors, and partial alveolus for the left canine, was found during paleontological explorations of karst-fill breccias in the Otavi region of northern Namibia. The mandible has unique characteristics that differentiate it from other middle Miocene hominoids of Africa and Eurasia and represents the only fossil evidence documenting a pre-australopithecine stage of hominoid evolution in southern Africa. Faunal analyses indicate that the breccia block containing the specimen accumulated during the latter part of the middle Miocene, about 13 +/- 1 Myr. Fauna from other breccia blocks at Berg Aukas are of diverse ages, including the earlier part of the middle Miocene, the upper Miocene, Plio-Pleistocene and Holocene. 相似文献
967.
A human recombinant haemoglobin designed for use as a blood substitute. 总被引:19,自引:0,他引:19
D Looker D Abbott-Brown P Cozart S Durfee S Hoffman A J Mathews J Miller-Roehrich S Shoemaker S Trimble G Fermi 《Nature》1992,356(6366):258-260
The need to develop a blood substitute is now urgent because of the increasing concern over blood-transmitted viral and bacterial pathogens. Cell-free haemoglobin solutions and human haemoglobin synthesized in Escherichia coli and Saccharomyces cerevisiae have been investigated as potential oxygen-carrying substitutes for red blood cells. But these haemoglobins cannot be used as a blood substitute because (1) the oxygen affinity in the absence of 2,3-bisphosphoglycerate is too high to allow unloading of enough oxygen in the tissues, and (2) they dissociate into alpha beta dimers that are cleared rapidly by renal filtration, which can result in long-term kidney damage. We have produced a human haemoglobin using an expression vector containing one gene encoding a mutant beta-globin with decreased oxygen affinity and one duplicated, tandemly fused alpha-globin gene. Fusion of the two alpha-globin subunits increases the half-life of this haemoglobin molecule in vivo by preventing its dissociation into alpha beta dimers and therefore also eliminates renal toxicity. 相似文献
968.
Susceptibility of beta 2-microglobulin-deficient mice to Trypanosoma cruzi infection. 总被引:8,自引:0,他引:8
The beta 2-microglobulin (beta 2m) protein associates with the products of the class I major histocompatibility (MHC) loci; this combination functions in the thymic development of and antigen presentation to CD8+ T cells. Mice in which the beta 2m gene has been disrupted by homologous recombination fail to express class I MHC gene products, and therefore lack CD8+ T cells and measurable cytotoxic T-cell responses. However, beta 2m- mice appear to have normal development of both CD4+ alpha/beta T-cell receptor (TCR+) and gamma/delta TCR+ T cells and are not overtly more susceptible than beta 2m+ mice to potential environmental agents of infection or to experimental viral infection. Here we show that beta 2m- mice suffer high parasitaemias and early death when infected with the obligate cytoplasmic protozoan parasite Trypanosoma cruzi. Despite this increased susceptibility, the beta 2m- mice are more responsive than their beta 2m+ littermates in terms of lymphokine production, making higher levels of both interleukin-2 and interferon-gamma in response to mitogen stimulation. In addition, the beta 2m- mice show essentially no inflammatory response in parasite-infected tissues. These results confirm previous experiments on mice depleted of CD8+ cells using antibody treatment in demonstrating the importance of CD8+ T cells in immune protection in T. cruzi infection. They also implicate CD8+ T cells and/or class I MHC molecules in regulation of lymphokine production and recruitment of inflammatory cells. 相似文献
969.
Normal dystrophin transcripts detected in Duchenne muscular dystrophy patients after myoblast transplantation. 总被引:26,自引:0,他引:26
E Gussoni G K Pavlath A M Lanctot K R Sharma R G Miller L Steinman H M Blau 《Nature》1992,356(6368):435-438
970.
Fusarium solani cutinase is a lipolytic enzyme with a catalytic serine accessible to solvent. 总被引:13,自引:0,他引:13
Lipases belong to a class of esterases whose activity on triglycerides is greatly enhanced at lipid-water interfaces. This phenomenon, called interfacial activation, has a structural explanation: a hydrophobic lid, which at rest covers the catalytic site, is displaced on substrate or inhibitor binding and probably interacts with the lipid matrix. Fusarium solani pisi cutinase belongs to a group of homologous enzymes of relative molecular mass 22-25K (ref. 7) capable of degrading cutin, the insoluble lipid-polyester matrix covering the surface of plants, and hydrolysing triglycerides. Cutinases differ from classical lipases in that they do not exhibit interfacial activation; they are active on soluble as well as on emulsified triglycerides. Cutinases therefore establish a bridge between esterases and lipases. We report here the three-dimensional structure of a recombinant cutinase from F. solani pisi, expressed in Escherichia coli. Cutinase is an alpha-beta protein; the active site is composed of the triad Ser 120, His 188 and Asp 175. Unlike other lipases, the catalytic serine is not buried under surface loops, but is accessible to solvent. This could explain why cutinase does not display interfacial activation. 相似文献