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201.
Farris AD Keech CL Gordon TP McCluskey J 《Cellular and molecular life sciences : CMLS》2000,57(4):569-578
Infectious microorganisms have evolved molecules which mimic the host in order to aid in their undetected propagation. In response, mammalian hosts have evolved a highly diverse immune repertoire designed to eradicate rapidly changing pathogens. The generation of diversity in the immune repertoire results in potentially damaging self cross-reactivities which require multiple regulatory controls to keep autoreactive lymphocytes in check. Here, we review how molecular mimicry at the T cell level might be important in the development of systemic autoimmunity. 相似文献
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Veiga-Fernandes H Coles MC Foster KE Patel A Williams A Natarajan D Barlow A Pachnis V Kioussis D 《Nature》2007,446(7135):547-551
Normal organogenesis requires co-ordinate development and interaction of multiple cell types, and is seemingly governed by tissue specific factors. Lymphoid organogenesis during embryonic life is dependent on molecules the temporal expression of which is tightly regulated. During this process, haematopoietic 'inducer' cells interact with stromal 'organizer' cells, giving rise to the lymphoid organ primordia. Here we show that the haematopoietic cells in the gut exhibit a random pattern of motility before aggregation into the primordia of Peyer's patches, a major component of the gut-associated lymphoid tissue. We further show that a CD45+CD4-CD3-Il7Ralpha-c-Kit+CD11c+ haematopoietic population expressing lymphotoxin has an important role in the formation of Peyer's patches. A subset of these cells expresses the receptor tyrosine kinase RET, which is essential for mammalian enteric nervous system formation. We demonstrate that RET signalling is also crucial for Peyer's patch formation. Functional genetic analysis revealed that Gfra3-deficiency results in impairment of Peyer's patch development, suggesting that the signalling axis RET/GFRalpha3/ARTN is involved in this process. To support this hypothesis, we show that the RET ligand ARTN is a strong attractant of gut haematopoietic cells, inducing the formation of ectopic Peyer's patch-like structures. Our work strongly suggests that the RET signalling pathway, by regulating the development of both the nervous and lymphoid system in the gut, has a key role in the molecular mechanisms that orchestrate intestine organogenesis. 相似文献
206.
Borg NA Wun KS Kjer-Nielsen L Wilce MC Pellicci DG Koh R Besra GS Bharadwaj M Godfrey DI McCluskey J Rossjohn J 《Nature》2007,448(7149):44-49
The CD1 family is a large cluster of non-polymorphic, major histocompatibility complex (MHC) class-I-like molecules that bind distinct lipid-based antigens that are recognized by T cells. The most studied group of T cells that interact with lipid antigens are natural killer T (NKT) cells, which characteristically express a semi-invariant T-cell receptor (NKT TCR) that specifically recognizes the CD1 family member, CD1d. NKT-cell-mediated recognition of the CD1d-antigen complex has been implicated in microbial immunity, tumour immunity, autoimmunity and allergy. Here we describe the structure of a human NKT TCR in complex with CD1d bound to the potent NKT-cell agonist alpha-galactosylceramide, the archetypal CD1d-restricted glycolipid. In contrast to T-cell receptor-peptide-antigen-MHC complexes, the NKT TCR docked parallel to, and at the extreme end of the CD1d-binding cleft, which enables a lock-and-key type interaction with the lipid antigen. The structure provides a basis for the interaction between the highly conserved NKT TCR alpha-chain and the CD1d-antigen complex that is typified in innate immunity, and also indicates how variability of the NKT TCR beta-chain can impact on recognition of other CD1d-antigen complexes. These findings provide direct insight into how a T-cell receptor recognizes a lipid-antigen-presenting molecule of the immune system. 相似文献
207.
Greenman C Stephens P Smith R Dalgliesh GL Hunter C Bignell G Davies H Teague J Butler A Stevens C Edkins S O'Meara S Vastrik I Schmidt EE Avis T Barthorpe S Bhamra G Buck G Choudhury B Clements J Cole J Dicks E Forbes S Gray K Halliday K Harrison R Hills K Hinton J Jenkinson A Jones D Menzies A Mironenko T Perry J Raine K Richardson D Shepherd R Small A Tofts C Varian J Webb T West S Widaa S Yates A Cahill DP Louis DN Goldstraw P Nicholson AG Brasseur F Looijenga L Weber BL Chiew YE DeFazio A 《Nature》2007,446(7132):153-158
Cancers arise owing to mutations in a subset of genes that confer growth advantage. The availability of the human genome sequence led us to propose that systematic resequencing of cancer genomes for mutations would lead to the discovery of many additional cancer genes. Here we report more than 1,000 somatic mutations found in 274 megabases (Mb) of DNA corresponding to the coding exons of 518 protein kinase genes in 210 diverse human cancers. There was substantial variation in the number and pattern of mutations in individual cancers reflecting different exposures, DNA repair defects and cellular origins. Most somatic mutations are likely to be 'passengers' that do not contribute to oncogenesis. However, there was evidence for 'driver' mutations contributing to the development of the cancers studied in approximately 120 genes. Systematic sequencing of cancer genomes therefore reveals the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated. 相似文献
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209.
Alison Adam 《Annals of science》2013,70(3):241-243
We study here the reception by their contemporaries of Antoine de Villon's and étienne de Clave's anti-Aristotelian, almost materialistic and atomistic theses, which they intended to support publicly in Paris in 1624, using (al)chemical experiments to this purpose. After surveying the intellectual context which could have then nourished an atomism based upon (al)chemical experiments, we go on to show how these theses, far from having been perceived as prominently atomistic, were condemned by the contemporaries above all because of the theological implications of their provocative anti-Aristotelism. Alchemy itself was not directly implicated in the case of the theses. On the contrary, the theses were perceived as an alien body within the alchemical tradition. 相似文献
210.
A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures 总被引:1,自引:0,他引:1
Sharp AJ Mefford HC Li K Baker C Skinner C Stevenson RE Schroer RJ Novara F De Gregori M Ciccone R Broomer A Casuga I Wang Y Xiao C Barbacioru C Gimelli G Bernardina BD Torniero C Giorda R Regan R Murday V Mansour S Fichera M Castiglia L Failla P Ventura M Jiang Z Cooper GM Knight SJ Romano C Zuffardi O Chen C Schwartz CE Eichler EE 《Nature genetics》2008,40(3):322-328
We report a recurrent microdeletion syndrome causing mental retardation, epilepsy and variable facial and digital dysmorphisms. We describe nine affected individuals, including six probands: two with de novo deletions, two who inherited the deletion from an affected parent and two with unknown inheritance. The proximal breakpoint of the largest deletion is contiguous with breakpoint 3 (BP3) of the Prader-Willi and Angelman syndrome region, extending 3.95 Mb distally to BP5. A smaller 1.5-Mb deletion has a proximal breakpoint within the larger deletion (BP4) and shares the same distal BP5. This recurrent 1.5-Mb deletion contains six genes, including a candidate gene for epilepsy (CHRNA7) that is probably responsible for the observed seizure phenotype. The BP4-BP5 region undergoes frequent inversion, suggesting a possible link between this inversion polymorphism and recurrent deletion. The frequency of these microdeletions in mental retardation cases is approximately 0.3% (6/2,082 tested), a prevalence comparable to that of Williams, Angelman and Prader-Willi syndromes. 相似文献