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611.
Scorpio A Blank TE Day WA Chabot DJ 《Cellular and molecular life sciences : CMLS》2006,63(19-20):2237-2248
Anthrax has been a major cause of death in grazing animals and an occasional cause of death in humans for thousands of years. Since the late 1800s there has been an exceptional international history of anthrax vaccine development. Due to animal vaccinations, the rate of infection has dropped dramatically. Anthrax vaccines have progressed from uncharacterized whole-cell vaccines in 1881, to pXO2-negative spores in the 1930s, to culture filtrates absorbed to aluminum hydroxide in 1970, and likely to recombinant protective antigen in the near future. Each of these refinements has increased safety without significant loss of efficacy. The threat of genetically engineered, antibiotic and vaccine resistant strains of Bacillus anthracis is fueling hypothesis-driven research and global techniques--including genomics, proteomics and transposon site hybridization--to facilitate the discovery of novel vaccine targets. This review highlights historical achievements and new developments in anthrax vaccine research. 相似文献
612.
Structural and biological aspects of carotenoid cleavage 总被引:1,自引:0,他引:1
Apo-carotenoid compounds such as retinol (vitamin A) are involved in a variety of cellular processes and are found in all kingdoms of life. Instead of being synthesized from small precursors, they are commonly produced by oxidative cleavage and subsequent modification of larger carotenoid compounds. The cleavage reaction is catalyzed by a family of related enzymes, which convert specific substrate double bonds to the corresponding aldehydes or ketones. The individual family members differ in their substrate preference and the position of the cleaved double bond, giving rise to a remarkable number of products starting from a limited number of carotenoid substrate molecules. The recent determination of the structure of a member of this family has provided insight into the reaction mechanism, showing how substrate specificity is achieved. This review will focus on the biochemistry of carotenoid oxygenases and the structural determinants of the cleavage reaction. 相似文献
613.
Valdar W Solberg LC Gauguier D Burnett S Klenerman P Cookson WO Taylor MS Rawlins JN Mott R Flint J 《Nature genetics》2006,38(8):879-887
Difficulties in fine-mapping quantitative trait loci (QTLs) are a major impediment to progress in the molecular dissection of complex traits in mice. Here we show that genome-wide high-resolution mapping of multiple phenotypes can be achieved using a stock of genetically heterogeneous mice. We developed a conservative and robust bootstrap analysis to map 843 QTLs with an average 95% confidence interval of 2.8 Mb. The QTLs contribute to variation in 97 traits, including models of human disease (asthma, type 2 diabetes mellitus, obesity and anxiety) as well as immunological, biochemical and hematological phenotypes. The genetic architecture of almost all phenotypes was complex, with many loci each contributing a small proportion to the total variance. Our data set, freely available at http://gscan.well.ox.ac.uk, provides an entry point to the functional characterization of genes involved in many complex traits. 相似文献
614.
Balasubramanian S Sureshkumar S Agrawal M Michael TP Wessinger C Maloof JN Clark R Warthmann N Chory J Weigel D 《Nature genetics》2006,38(6):711-715
Light has an important role in modulating seedling growth and flowering time. We show that allelic variation at the PHYTOCHROME C (PHYC) photoreceptor locus affects both traits in natural populations of A. thaliana. Two functionally distinct PHYC haplotype groups are distributed in a latitudinal cline dependent on FRIGIDA, a locus that together with FLOWERING LOCUS C explains a large portion of the variation in A. thaliana flowering time. In a genome-wide scan for association of 65 loci with latitude, there was an excess of significant P values, indicative of population structure. Nevertheless, PHYC was the most strongly associated locus across 163 strains, suggesting that PHYC alleles are under diversifying selection in A. thaliana. Our work, together with previous findings, suggests that photoreceptor genes are major agents of natural variation in plant flowering and growth response. 相似文献
615.
616.
617.
Huet J Wyckmans J Wintjens R Boussard P Raussens V Vandenbussche G Ruysschaert JM Azarkan M Looze Y 《Cellular and molecular life sciences : CMLS》2006,63(24):3042-3054
Two chitinases, able to use tetra-N-acetylglucosamine, chitin and chitosan as substrates, were characterized after purification from Carica papaya latex. The complete amino acid sequence of the major form and about 40% of the minor one were determined through proteolytic
digestions and mass spectroscopy analysis. Sequencing demonstrated that both papaya chitinases are members of the family 19
of glycosyl hydrolases (GH19). Based on the known 3-D structures of other members of family GH19, it was expected that papaya
chitinases would adopt all-alpha structures. However, circular dichroism and infrared spectroscopy indicated, for the papaya
chitinases, a content of 15–20% of extended structures besides the expected 40% of alpha helices. Since the fully sequenced
papaya chitinase contains a large number of proline residues the possibility that papaya chitinase contains polyproline II
stretches was examined in the context of their resistance against proteolytic degradation.
Received 11 July 2006; received after revision 13 October 2006; accepted 25 October 2006 相似文献
618.
Kramer J Böhrnsen F Lindner U Behrens P Schlenke P Rohwedel J 《Cellular and molecular life sciences : CMLS》2006,63(5):616-626
Microfracture of subchondral bone results in intrinsic repair of cartilage defects. Stem or progenitor cells from bone marrow
have been proposed to be involved in this regenerative process. Here, we demonstrate for the first time that mesenchymal stem
(MS) cells can in fact be recovered from matrix material saturated with cells from bone marrow after microfracture. This also
introduces a new technique for MS cell isolation during arthroscopic treatment. MS cells were phenotyped using specific cell
surface antibodies. Differentiation of the MS cells into the adipogenic, chondrogenic and osteogenic lineage could be demonstrated
by cultivation of MS cells as a monolayer, as micromass bodies or mesenchymal microspheres. This study demonstrates that MS
cells can be attracted to a cartilage defect by guidance of a collagenous matrix after perforating subchondral bone. Protocols
for application of MS cells in restoration of cartilage tissue include an initial invasive biopsy to obtain the MS cells and
time-wasting in vitro proliferation and possibly differentiation of the cells before implantation. The new technique already includes attraction
of MS cells to sites of cartilage defects and therefore may overcome the necessity of in vitro proliferation and differentiation of MS cells prior to transplantation.
Received 3 November 2005; received after revision 15 December 2005; accepted 4 January 2006 相似文献
619.
Pappas G Panagopoulou P Christou L Akritidis N 《Cellular and molecular life sciences : CMLS》2006,63(19-20):2229-2236
Brucella has traditionally been considered a biological weapon. It was the subject of extensive offensive research in the past, and still belongs to category B pathogens on most lists. Its propensity for airborne transmission and induction of chronic debilitating disease requiring combined antibiotic regimens for treatment, its abundance around the world and its vague clinical characteristics defying rapid clinical diagnosis are some of the characteristics that apply to the pathogen's weapons potential. Yet minimal mortality, availability of treatment options, protracted inoculation period and the emergence of new, more virulent potential weapons means that its inclusion among agents of bioterrorism is nowadays mainly of historical significance. Nevertheless, in the interest of literacy and of avoiding panic, physicians and the public both should be aware of the most common zoonosis worldwide. 相似文献
620.
Identification of rate-limiting steps or components of intracellular second messenger systems holds promise to effectively
interfere with these pathways under pathological conditions. The emerging literature on a recently identified family of signalling
regulator proteins, called tribbles gives interesting clues for how these proteins seem to link several ‘independent’ signal
processing systems together. Via their unique way of action, tribbles co-ordinate the activation and suppression of the various
interacting signalling pathways and therefore appear to be key in determining cell fate while responding to environmental
challenges. This review summarises our current understanding of tribbles function and also provides an evolutionary perspective
on the various tribbles genes.
Received 10 January 2006; received after revision 20 March 2006; accepted 5 April 2006 相似文献