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941.
Sato T van Es JH Snippert HJ Stange DE Vries RG van den Born M Barker N Shroyer NF van de Wetering M Clevers H 《Nature》2011,469(7330):415-418
Homeostasis of self-renewing small intestinal crypts results from neutral competition between Lgr5 stem cells, which are small cycling cells located at crypt bottoms. Lgr5 stem cells are interspersed between terminally differentiated Paneth cells that are known to produce bactericidal products such as lysozyme and cryptdins/defensins. Single Lgr5-expressing stem cells can be cultured to form long-lived, self-organizing crypt-villus organoids in the absence of non-epithelial niche cells. Here we find a close physical association of Lgr5 stem cells with Paneth cells in mice, both in vivo and in vitro. CD24(+) Paneth cells express EGF, TGF-α, Wnt3 and the Notch ligand Dll4, all essential signals for stem-cell maintenance in culture. Co-culturing of sorted stem cells with Paneth cells markedly improves organoid formation. This Paneth cell requirement can be substituted by a pulse of exogenous Wnt. Genetic removal of Paneth cells in vivo results in the concomitant loss of Lgr5 stem cells. In colon crypts, CD24(+) cells residing between Lgr5 stem cells may represent the Paneth cell equivalents. We conclude that Lgr5 stem cells compete for essential niche signals provided by a specialized daughter cell, the Paneth cell. 相似文献
942.
Gieger C Radhakrishnan A Cvejic A Tang W Porcu E Pistis G Serbanovic-Canic J Elling U Goodall AH Labrune Y Lopez LM Mägi R Meacham S Okada Y Pirastu N Sorice R Teumer A Voss K Zhang W Ramirez-Solis R Bis JC Ellinghaus D Gögele M Hottenga JJ Langenberg C Kovacs P O'Reilly PF Shin SY Esko T Hartiala J Kanoni S Murgia F Parsa A Stephens J van der Harst P Ellen van der Schoot C Allayee H Attwood A Balkau B Bastardot F Basu S Baumeister SE Biino G Bomba L Bonnefond A Cambien F Chambers JC Cucca F 《Nature》2011,480(7376):201-208
Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function. 相似文献
943.
Keane TM Goodstadt L Danecek P White MA Wong K Yalcin B Heger A Agam A Slater G Goodson M Furlotte NA Eskin E Nellåker C Whitley H Cleak J Janowitz D Hernandez-Pliego P Edwards A Belgard TG Oliver PL McIntyre RE Bhomra A Nicod J Gan X Yuan W van der Weyden L Steward CA Bala S Stalker J Mott R Durbin R Jackson IJ Czechanski A Guerra-Assunção JA Donahue LR Reinholdt LG Payseur BA Ponting CP Birney E Flint J Adams DJ 《Nature》2011,477(7364):289-294
944.
Smeulders MJ Barends TR Pol A Scherer A Zandvoort MH Udvarhelyi A Khadem AF Menzel A Hermans J Shoeman RL Wessels HJ van den Heuvel LP Russ L Schlichting I Jetten MS Op den Camp HJ 《Nature》2011,478(7369):412-416
Extremophilic organisms require specialized enzymes for their exotic metabolisms. Acid-loving thermophilic Archaea that live in the mudpots of volcanic solfataras obtain their energy from reduced sulphur compounds such as hydrogen sulphide (H(2)S) and carbon disulphide (CS(2)). The oxidation of these compounds into sulphuric acid creates the extremely acidic environment that characterizes solfataras. The hyperthermophilic Acidianus strain A1-3, which was isolated from the fumarolic, ancient sauna building at the Solfatara volcano (Naples, Italy), was shown to rapidly convert CS(2) into H(2)S and carbon dioxide (CO(2)), but nothing has been known about the modes of action and the evolution of the enzyme(s) involved. Here we describe the structure, the proposed mechanism and evolution of a CS(2) hydrolase from Acidianus A1-3. The enzyme monomer displays a typical β-carbonic anhydrase fold and active site, yet CO(2) is not one of its substrates. Owing to large carboxy- and amino-terminal arms, an unusual hexadecameric catenane oligomer has evolved. This structure results in the blocking of the entrance to the active site that is found in canonical β-carbonic anhydrases and the formation of a single 15-?-long, highly hydrophobic tunnel that functions as a specificity filter. The tunnel determines the enzyme's substrate specificity for CS(2), which is hydrophobic. The transposon sequences that surround the gene encoding this CS(2) hydrolase point to horizontal gene transfer as a mechanism for its acquisition during evolution. Our results show how the ancient β-carbonic anhydrase, which is central to global carbon metabolism, was transformed by divergent evolution into a crucial enzyme in CS(2) metabolism. 相似文献
945.
Bouwens RJ Illingworth GD Labbe I Oesch PA Trenti M Carollo CM van Dokkum PG Franx M Stiavelli M González V Magee D Bradley L 《Nature》2011,469(7331):504-507
Searches for very-high-redshift galaxies over the past decade have yielded a large sample of more than 6,000 galaxies existing just 900-2,000?million years (Myr) after the Big Bang (redshifts 6?>?z?>?3; ref. 1). The Hubble Ultra Deep Field (HUDF09) data have yielded the first reliable detections of z?≈?8 galaxies that, together with reports of a γ-ray burst at z?≈?8.2 (refs 10, 11), constitute the earliest objects reliably reported to date. Observations of z?≈?7-8 galaxies suggest substantial star formation at z?>?9-10 (refs 12, 13). Here we use the full two-year HUDF09 data to conduct an ultra-deep search for z?≈?10 galaxies in the heart of the reionization epoch, only 500?Myr after the Big Bang. Not only do we find one possible z?≈?10 galaxy candidate, but we show that, regardless of source detections, the star formation rate density is much smaller (~10%) at this time than it is just ~200?Myr later at z?≈?8. This demonstrates how rapid galaxy build-up was at z?≈?10, as galaxies increased in both luminosity density and volume density from z?≈?10 to z?≈?8. The 100-200?Myr before z?≈?10 is clearly a crucial phase in the assembly of the earliest galaxies. 相似文献
946.
947.
Résumé La streptomycine et les acridines ont une propriété commune, en ce qu'ils forment avec les nucléoprotéides des levures de complexes électro-adsorptifs. 相似文献
948.
L. Massart G. Peeters J. de Ley R. Vercauteren A. van Houcke 《Cellular and molecular life sciences : CMLS》1947,3(7):288-289
Résumé Les acridines forment avec les nucléoprotéides des levures, des complexes électro-adsorptifs. Le pouvoir bactéricide des acridines s'exerce par une compétition entre les ion H+ de ce complexe et l'ion acridine. Différents enzymes activés par des ions métalliques doivent leur activité catalytique au même type de complexes. Les acridines inhibent ces enzymes parce qu'ils déplacent le cathion métallique. 相似文献
949.
Summary A survey of recent work on the theories of the peculiar mechanical behaviour of substances with rubber-like properties is given. All the theories are based on the assumption that these substances (including rubber itself) are composed of very long, flexible chainmolecules. Any segment of a chain is linked to two neighbouring segments by bonds similar to those which are present in typical solids and to all other neighbours by linkages like the bonds prevailing between the particles of liquids. The chain molecules are intermingled so as to form a kind of a felt.This state of aggregation is intermediate between the solid and the liquid; it is called the rubber-like state (état gommoïdal). Elasticity, viscosity and plastic flow as well as the influence of crystallization, vulcanization and degradation are discussed in terms of this theory. 相似文献
950.