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101.
A role for the human DNA repair enzyme HAP1 in cellular protection against DNA damaging agents and hypoxic stress. 总被引:14,自引:5,他引:9 下载免费PDF全文
The HAP1 protein (also known as APE/Ref-1) is a bifunctional human nuclear enzyme required for repair of apurinic/apyrimidinic sites in DNA and reactivation of oxidized proto-oncogene products. To gain insight into the biological roles of HAP1, the effect of expressing antisense HAP1 RNA in HeLa cells was determined. The constructs for antisense RNA expression consisted of either a full-length HAP1 cDNA or a genomic DNA fragment cloned downstream of the CMV promoter in pcDNAneo. Stable HeLa cell transfectants expressing HAP1 antisense RNA were found to express greatly reduced levels of the HAP1 protein compared to equivalent sense orientation and vector-only control transfectants. The antisense HAP1 transfectants exhibited a normal growth rate, cell morphology and plating efficiency, but were hypersensitive to killing by a wide range of DNA damaging agents, including methyl methanesulphonate, hydrogen peroxide, menadione, and paraquat. However, survival after UV irradiation was unchanged. The antisense transfectants were strikingly sensitive to changes in oxygen tension, exhibiting increased killing compared to controls following exposure to both hypoxia (1% oxygen) and hyperoxia (100% oxygen). Consistent with a requirement for HAP1 in protection against hypoxic stress, expression of the HAP1 protein was found to be induced in a time-dependent manner in human cells during growth under 1% oxygen. The possible involvement of a depletion of cellular glutathione being linked to the hypoxic stress-sensitive phenotype of the antisense HAP1 transfectants came from the finding that they also exhibited hypersensitivity to buthionine sulphoximine, an inhibitor of glutathione biosynthesis. We conclude that the HAP1 protein is a key factor in cellular protection against a wide variety of cellular stresses, including DNA damage and a change in oxygen tension. 相似文献
102.
Katherine Coffing Craig Feibel Meave Leakey Alan Walker 《American journal of physical anthropology》1994,93(1):55-65
A piece of mandible and several isolated teeth are reported from fluviatile sediments older than 4 million years at East Lake Turkana. They most closely resemble hominids from Laetoli, Tanzania and Hadar, Ethiopia which have been assigned to Australopithecus afarensis. © 1994 Wiley-Liss, Inc. 相似文献
103.
Richard W. Hyman Susan Frank Craig H. Warden Aaron Daluiski Renu Heller Aldons J. Lusis 《Biochemical genetics》1994,32(11-12):397-407
Quantitative trait locus (QTL) analysis is a statistical method that can be applied to identify loci making a significant impact on a phenotype. For the phenotype of susceptibility to diet-induced atherosclerosis in the mouse, we have studied four quantitative traits: area of aortic fatty streaks and serum concentrations of high-density lipoprotein-bound cholesterol (HDL-cholesterol), apolipoprotein A-I, and apolipoprotein A-II (apo A-II). QTL analysis revealed a significant locus on chromosome 1 distal impacting serum apo A-II concentration on a high-fat diet and serum HDL-cholesterol concentration on a chow diet. This locus is presumablyApoa-2, the structural gene for apo A-II. QTL analysis of aortic fatty streaks failed to reveal a significant locus. 相似文献
104.
Catherine L. Craig Gary D. Bernard Jonathan A. Coddington 《Evolution; international journal of organic evolution》1994,48(2):287-296
We measured the reflectance properties of unpigmented silks spun by a systematic array of primitive (Deinopoidea) and derived (Araneoidea) aerial, web-spinning spiders, as well as silks spun by Araneomorphae and Mygalomorphae spiders that do not spin aerial webs. Our data show that all of the primitive aerial web spinners produce catching silks with a spectral peak in the ultraviolet (UV), and cladistic analysis suggests that high UV reflection is the primitive character state for silk spectral properties. In contrast, all of the derived aerial web spinners produce silks that are spectrally flat or characterized by reduced reflectance in the UV. Correlated with the evolution of these catching silks is a 37-fold increase in species number and apparent habitat expansion. This suggests that the unique silk proteins spun by the araneoids have been important to their ecological and evolutionary diversity. 相似文献
105.
Molecular evolution of the HSP70 multigene family 总被引:38,自引:0,他引:38
William R. Boorstein Thomas Ziegelhoffer Elizabeth A. Craig 《Journal of molecular evolution》1994,38(1):1-17
Eukaryotic genomes encode multiple 70-kDa heat-shock proteins (HSP70s). The Saccharomyces cerevisiae HSP70 family is comprised of eight members. Here we present the nucleotide sequence of the SSA3 and SSB2 genes, completing the nucleotide sequence data for the yeast HSP70 family. We have analyzed these yeast sequences as well as 29 HSP70s from 24 additional eukaryotic and prokaryotic species. Comparison of the sequences demonstrates the extreme conservation of HSP70s; proteins from the most distantly related species share at least 45% identity and more than one-sixth of the amino acids are identical in the aligned region (567 amino acids) among all proteins analyzed. Phylogenetic trees constructed by two independent methods indicate that ancient molecular and cellular events have given rise to at least four monophyletic groups of eukaryotic HSP70 proteins. Each group of evolutionarily similar HSP70s shares a common intracellular localization and is presumed to be comprised of functional homologues; these include heat-shock proteins of the cytoplasm, endoplasmic reticulum, mitochondria, and chloroplasts. HSP70s localized in mitochondria and plastids are most similar to the DnaK HSP70 homologues in purple bacteria and cyanobacteria, respectively, which is consistent with the proposed prokaryotic origin of these organelles. The analyses indicate that the major eukaryotic HSP70 groups arose prior to the divergence of the earliest eukaryotes, roughly 2 billion years ago. In some cases, as exemplified by the SSA genes encoding the cytoplasmic HSP70s of S. cerevisiae, more recent duplication events have given rise to subfamilies within the major groups. The S. cerevisiae SSB proteins comprise a unique subfamily not identified in other species to date. This subfamily appears to have resulted from an ancient gene duplication that occurred at approximately the same time as the origin of the major eukaryotic HSP70 groups.
Correspondence to: E.A. Craig 相似文献
106.
A. M. Chaudhury S. Craig E. S. Dennis M. Lavithis P. E. Taylor M. B. Singh R. B. Knox E. R. Signer 《Sexual plant reproduction》1994,7(1):17-28
We have taken a mutational approach to identify genes important for male fertility in Arabidopsis thaliana and have isolated a number of nuclear male/ sterile mutants in which vegetative growth and female fertility are not altered. Here we describe detailed developmental analyses of four mutants, each of which defines a complementation group and has a distinct developmental end point. All four mutants represent premeiotic developmental lesions. In ms3, tapetum and middle layer hypertrophy result in the degeneration of microsporocytes. In ms4, microspore dyads persist for most of anther development as a result of impaired meiotic division. In ms5, degeneration occurs in all anther cells at an early stage of development. In ms15, both the tapetum and microsporocytes degenerate early in anther development. Each of these mutants had shorter filaments and a greater number of inflorescences than congenic male-fertile plants. The differences in the developmental phenotypes of these mutants, together with the non-allelic nature of the mutations indicate that four different genes important for pollen development, have been identified. 相似文献
107.
Cloning of the nupC gene of Escherichia coli encoding a nucleoside transport system, and identification of an adjacent Insertion element, IS 186 总被引:1,自引:0,他引:1
Escherichia coli is known to contain more than one active transport system for nucleoside uptake. In the present study we report the sequence of a gene encoding a second nucleoside transport system, nupC (in addition to nupG.) An open reading frame (ORF) of 1200bp was identified that codes for a hydrophobic polypeptide of 43 560 Da and an NupC fusion protein was shown to be membrane associated. The native NupC protein is also identified, following over-expression. NupC exhibits short regions of homology to several membrane-associated proteins, including LacY and Cyd. Analysis of the nupC promoter region revealed the presence of at least two putative CRP-binding sites, centred at–40bp and–89bp, which probably flank a CytR-binding site. In addition, an adjacent IS186 element was identified and found to reside within a putative terminator structure, downstream from the nupC ORF. This arrangement is shown to reflect the previously established gene order on the E. coli chromosome. 相似文献
108.
Metabolic engineering of plant secondary products 总被引:5,自引:0,他引:5
Craig L. Nessler 《Transgenic research》1994,3(2):109-115
Plants interact with their environment by producing a diverse array of secondary metabolites. Many of these compounds are valued for their medicinal, industrial or agricultural properties. Other secondary products are toxic or otherwise undesirable and can reduce the commercial value of crops. Gene transfer technology offers new opportunities to modify directly plant secondary product synthesis through metabolic engineering. This article reviews some of the strategies which have been used to increase or decrease the synthesis of specific plant metabolites, as well as methods for expanding the biosynthetic capabilities of individual species. 相似文献
109.
The effect of an acute increase in temperature, exhaustive exercise and hypoxia on the haematology of the benthic Antarctic teleost, Trematomus bernacchii was investigated. High temperature and hypoxia caused the biggest changes to the blood, with increases in haematocrit, haemoglobin concentrations and plasma chloride levels. The spleen decreased in mass. Exercise produced the smallest changes. Changes were substantially less than reported for the more active cryopelagic species Pagothenia borchgrevinki. The magnitude of the haematocrit increase is discussed in relation to life-style of fish living in the Antarctic. 相似文献
110.
Glutamate receptors mediate the majority of excitatory neurotransmission in the brain, and molecular cloning studies have revealed several distinct families. Because neuropathological states and possibly human disorders may involve kainate-preferring glutamate receptors, we have isolated a cDNA clone for the human GluR6 kainate-preferring receptor. This clone shows a very high sequence similarity with that of the rat, except for a part of the 3′ untranslated region in which there is a TAA triplet repeat. When the protein was overexpressed in human embryonic kidney 293 cells, it had a molecular weight, an antibody recognition, and a glutamate ligand-binding profile similar to those of the rat GluR6 receptor. Northern analysis showed expression in both human cerebral and cerebellar cortices. By PCR analysis of rodent-human monochromosomal cell lines, the human GluR6 could be assigned to chromosome 6. The length of the TAA triplet repeat was polymorphic in the normal population, with at least four alleles and an observed heterozygosity of about 45%. These studies should provide the basis for expression or linkage studies of the GluR6 kainate receptor in human disease or neuropathologic states. 相似文献