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991.
Differential arrangements of conserved building blocks among homologs of the Rad50/Mre11 DNA repair protein complex 总被引:5,自引:0,他引:5
de Jager M Trujillo KM Sung P Hopfner KP Carney JP Tainer JA Connelly JC Leach DR Kanaar R Wyman C 《Journal of molecular biology》2004,339(4):937-949
Structural maintenance of chromosomes (SMC) proteins have diverse cellular functions including chromosome segregation, condensation and DNA repair. They are grouped based on a conserved set of distinct structural motifs. All SMC proteins are predicted to have a bipartite ATPase domain that is separated by a long region predicted to form a coiled coil. Recent structural data on a variety of SMC proteins shows them to be arranged as long intramolecular coiled coils with a globular ATPase at one end. SMC proteins function in pairs as heterodimers or as homodimers often in complexes with other proteins. We expect the arrangement of the SMC protein domains in complex assemblies to have important implications for their diverse functions. We used scanning force microscopy imaging to determine the architecture of human, Saccharomyces cerevisiae, and Pyrococcus furiosus Rad50/Mre11, Escherichia coli SbcCD, and S.cerevisiae SMC1/SMC3 cohesin SMC complexes. Two distinct architectural arrangements are described, based on the way their components were connected. The eukaryotic complexes were similar to each other and differed from their prokaryotic and archaeal homologs. These similarities and differences are discussed with respect to their diverse mechanistic roles in chromosome metabolism. 相似文献
992.
In protein-coding DNA sequences, historical patterns of selection can be inferred from amino acid substitution patterns. High relative rates of nonsynonymous to synonymous changes (=d
N
/d
S
) are a clear indicator of positive, or directional, selection, and several recently developed methods attempt to distinguish these sites from those under neutral or purifying selection. One method uses an empirical Bayesian framework that accounts for varying selective pressures across sites while conditioning on the parameters of the model of DNA evolution and on the phylogenetic history. We describe a method that identifies sites under diversifying selection using a fully Bayesian framework. Similar to earlier work, the method presented here allows the rate of nonsynonymous to synonymous changes to vary among sites. The significant difference in using a fully Bayesian approach lies in our ability to account for uncertainty in parameters including the tree topology, branch lengths, and the codon model of DNA substitution. We demonstrate the utility of the fully Bayesian approach by applying our method to a data set of the vertebrate -globin gene. Compared to a previous analysis of this data set, the hierarchical model found most of the same sites to be in the positive selection class, but with a few striking exceptions. 相似文献
993.
West M Mhatre M Ceballos A Floyd RA Grammas P Gabbita SP Hamdheydari L Mai T Mou S Pye QN Stewart C West S Williamson KS Zemlan F Hensley K 《Journal of neurochemistry》2004,91(1):133-143
Familial forms of amyotrophic lateral sclerosis (ALS) can be caused by mutations in copper, zinc-superoxide dismutase (SOD1). Mice expressing SOD1 mutants demonstrate a robust neuroinflammatory reaction characterized, in part, by up-regulation of tumor necrosis factor alpha (TNFalpha) and its primary receptor TNF-RI. In an effort to identify small molecule inhibitors of neuroinflammation useful in treatment of ALS, a microglial culture system was established to identify TNFalpha antagonists. Walker EOC-20 microglia cells were stimulated with recombinant TNFalpha, with or without inhibitors, and the cell response was indexed by NO2- output. Three hundred and fifty-five rationally selected compounds were included in this bioassay. The arachidonic acid 5-lipoxygenase (5LOX) and tyrosine kinase inhibitor nordihydroguaiaretic acid (NDGA), a natural dicatechol, was one of the most potent non-cytotoxic antagonists tested (IC50 8 +/- 3 microm). Investigation of the G93A-SOD1 mouse model for ALS revealed increased message and protein levels of 5LOX at 120 days of age. Oral NDGA (2500 p.p.m.) significantly extended lifespan and slowed motor dysfunction in this mouse, when administration was begun relatively late in life (90 days). NDGA extended median total lifespan of G93A-SOD1 mice by 10%, and life expectancy following start of treatment was extended by 32%. Disease-associated gliosis and cleaved microtubule-associated tau protein, an indicator of axon damage, were likewise reduced by NDGA. Thus, TNFalpha antagonists and especially 5LOX inhibitors might offer new opportunities for treatment of ALS. 相似文献
994.
Exposure of selected Gram-positive and Gram-negative bacterial pathogens to egg shell membranes (ESM) significantly reduced
their thermal resistance and/or inactivated cells. Although the components responsible for this antibacterial activity have
not been conclusively identified, several proteins associated with the ESM activity have been identified including β-N-acetylglucosaminidase,
lysozyme and ovotransferrin, with each displaying varying degrees of antibacterial activity. Numerous attempts to purify active
fractions of β-N-acetylglucosaminidase, lysozyme and ovotransferrin from the ESM proved somewhat limited; however, hen egg
white (HEW) β-N-acetylglucosaminidase was purified using a two-step chromatographic procedure, isoelectric focusing followed
by cation exchange chromatography. Pure fractions of ovotransferrin were also obtained in the process. SDS-PAGE electrophoresis
and Matrix-Assisted Laser Desorption Time-of-Flight Mass Spectrometry were then used to partially characterize the individual
protein components. Purified protein fractions such as these will be required in order to fully elucidate the mechanism responsible
for the antimicrobial properties associated with the ESM. 相似文献
995.
Previous investigations of bovine seminal plasma (BSP) have revealed the identities of the three major proteins, BSP-PDC109, BSP-A3 and BSP-30 kDa, which together constitute about half of the total protein, as well as about 30 of the minor proteins. Analyses of BSP by 2-DE have revealed about 250 protein spots, suggesting that much of the BSP proteome remains undescribed. In this study, BSP has been analyzed by 2-D LC-based and SDS-PAGE-based proteomic methods. Ninety-nine proteins were identified, including 49 minor proteins that have not previously been described in seminal plasma of any species. 相似文献
996.
997.
Yvonne J.K. Edwards Klaudia Walter Gayle McEwen Tanya Vavouri Krystyna A. Kelly Irina Abnizova Adam Woolfe Debbie K. Goode Martin Goodson Phil North Phil Snell Heather Callaway Sarah F. Smith Walter R. Gilks Julie E. Cooke Greg Elgar 《Comparative biochemistry and physiology. Part D, Genomics & proteomics》2006,1(1):46
998.
ZNF652, a novel zinc finger protein, interacts with the putative breast tumor suppressor CBFA2T3 to repress transcription 总被引:2,自引:0,他引:2
999.
1000.
Brendan P. Kelly Oriana H. Badajos Mervi Kunnasranta John R. Moran Micaela Martinez-Bakker Douglas Wartzok Peter Boveng 《Polar Biology》2010,33(8):1095-1109
Population structure and patterns of habitat use among ringed seals (Phoca hispida) are poorly known, in part because seasonal movements have not been adequately documented. We monitored the movements of
98 ringed seals in the Beaufort and Chukchi seas between 1990 and 2006 using three forms of telemetry. In the winter—spring
period (when the seals were occupying shorefast ice), we used radio and ultra-sonic tags to track movements above and below
the ice, respectively. We used satellite-linked transmitters in summer and fall (when the seals ranged away from their winter
sites) to track at-sea movements. In the shorefast ice habitat, the home ranges of 27 adult males ranged from <1 to 13.9 km2 (median = 0.628) while the home ranges of 28 adult females ranged from <1 to 27.9 km2 (median = 0.652). The 3-dimensional volumes used by 9 seals tracked acoustically under the ice averaged 0.07 (SD = 0.04) km3 for subadults and adult males and 0.13 (SD = 0.04) km3 for adult females. Three of the radio-tracked seals and 9 tracked by satellite ranged up to 1,800 km from their winter/spring
home ranges in summer but returned to the same small (1–2 km2) sites during the ice-bound months in the following year. The restricted movements of ringed seals during the ice-bound season—including
the breeding season—limits their foraging activities for most of the year and may minimize gene flow within the species. 相似文献