全文获取类型
收费全文 | 12136篇 |
免费 | 1154篇 |
国内免费 | 1篇 |
出版年
2023年 | 43篇 |
2022年 | 122篇 |
2021年 | 268篇 |
2020年 | 141篇 |
2019年 | 182篇 |
2018年 | 223篇 |
2017年 | 209篇 |
2016年 | 337篇 |
2015年 | 583篇 |
2014年 | 620篇 |
2013年 | 664篇 |
2012年 | 909篇 |
2011年 | 868篇 |
2010年 | 548篇 |
2009年 | 514篇 |
2008年 | 670篇 |
2007年 | 680篇 |
2006年 | 645篇 |
2005年 | 657篇 |
2004年 | 591篇 |
2003年 | 583篇 |
2002年 | 523篇 |
2001年 | 155篇 |
2000年 | 126篇 |
1999年 | 172篇 |
1998年 | 149篇 |
1997年 | 110篇 |
1996年 | 89篇 |
1995年 | 97篇 |
1994年 | 89篇 |
1993年 | 84篇 |
1992年 | 103篇 |
1991年 | 105篇 |
1990年 | 100篇 |
1989年 | 109篇 |
1988年 | 89篇 |
1987年 | 85篇 |
1986年 | 66篇 |
1985年 | 59篇 |
1984年 | 79篇 |
1983年 | 52篇 |
1982年 | 47篇 |
1981年 | 39篇 |
1980年 | 41篇 |
1979年 | 55篇 |
1978年 | 54篇 |
1976年 | 42篇 |
1974年 | 44篇 |
1973年 | 41篇 |
1972年 | 33篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
991.
Caloric restriction and genomic stability 总被引:1,自引:0,他引:1
Caloric restriction (CR) reduces the incidence and progression of spontaneous and induced tumors in laboratory rodents while increasing mean and maximum life spans. It has been suggested that CR extends longevity and reduces age-related pathologies by reducing the levels of DNA damage and mutations that accumulate with age. This hypothesis is attractive because the integrity of the genome is essential to a cell/organism and because it is supported by observations that both cancer and immunological defects, which increase significantly with age and are delayed by CR, are associated with changes in DNA damage and/or DNA repair. Over the last three decades, numerous laboratories have examined the effects of CR on the integrity of the genome and the ability of cells to repair DNA. The majority of studies performed indicate that the age-related increase in oxidative damage to DNA is significantly reduced by CR. Early studies suggest that CR reduces DNA damage by enhancing DNA repair. With the advent of genomic technology and our increased understanding of specific repair pathways, CR has been shown to have a significant effect on major DNA repair pathways, such as NER, BER and double-strand break repair. 相似文献
992.
Aerobic Anoxygenic Phototrophic Bacteria Attached to Particles in Turbid Waters of the Delaware and Chesapeake Estuaries 总被引:3,自引:0,他引:3
下载免费PDF全文
![点击此处可从《Applied microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Aerobic anoxygenic phototrophic (AAP) bacteria are photoheterotrophs that, if abundant, may be biogeochemically important in the oceans. We used epifluorescence microscopy and quantitative PCR (qPCR) to examine the abundance of these bacteria by enumerating cells with bacteriochlorophyll a (bChl a) and the light-reaction center gene pufM, respectively. In the surface waters of the Delaware estuary, AAP bacteria were abundant, comprising up to 34% of prokaryotes, although the percentage varied greatly with location and season. On average, AAP bacteria made up 12% of the community as measured by microscopy and 17% by qPCR. In the surface waters of the Chesapeake, AAP bacteria were less abundant, averaging 6% of prokaryotes. AAP bacterial abundance was significantly correlated with light attenuation (r = 0.50) and ammonium (r = 0.42) and nitrate (r = 0.71) concentrations. Often, bChl a-containing bacteria were mostly attached to particles (31 to 94% of total AAP bacteria), while usually 20% or less of total prokaryotes were associated with particles. Of the cells containing pufM, up to 87% were associated with particles, but the overall average of particle-attached cells was 15%. These data suggest that AAP bacteria are particularly competitive in these two estuaries, in part due to attachment to particles. 相似文献
993.
Yaoyu Feng Kerri A. Alderisio Wenli Yang Lisa A. Blancero William G. Kuhne Christopher A. Nadareski Michael Reid Lihua Xiao 《Applied microbiology》2007,73(20):6475-6483
To identify the animal sources for Cryptosporidium contamination, we genotyped Cryptosporidium spp. in wildlife from the watershed of the New York City drinking water supply, using a small-subunit rRNA gene-based PCR-restriction fragment length polymorphism analysis and DNA sequencing. A total of 541 specimens from 38 species of wildlife were analyzed. One hundred and eleven (20.5%) of the wildlife specimens were PCR positive. Altogether, 21 Cryptosporidium genotypes were found in wildlife samples, 11 of which were previously found in storm runoff in the watershed, and six of these 11 were from storm water genotypes of unknown animal origin. Four new genotypes were found, and the animal hosts for four storm water genotypes were expanded. With the exception of the cervine genotype, most genotypes were found in a limited number of animal species and have no major public health significance. 相似文献
994.
Comuzzie AG Tejero ME Funahashi T Martin LJ Kissebah A Takahashi M Kihara S Tanaka S Rainwater DL Matsuzawa Y MacCluer JW Blangero J 《Human biology; an international record of research》2007,79(2):191-200
Results from previous studies suggest that adiponectin levels are associated with risk factors for cardiovascular disease and type 2 diabetes mellitus; however, the genetic and/or environmental components of this relationship have not been characterized. The aims of this study were (1) to assess the presence of pleiotropy between adiponectin levels and risk factors for cardiovascular disease and (2) to study the association of circulating levels of adiponectin with risk factors for cardiovascular disease in the absence and presence of obesity in Mexican American adults from the San Antonio Family Heart Study. Body composition and circulating levels of adiponectin, leptin, and lipid subfractions and measurements of glucose metabolism were measured in 898 subjects. The mean and standard error of the circulating levels of adiponectin was 8.7 +/- 3.2 microg/ml. Bivariate quantitative analyses between adiponectin levels and phenotypes related to cardiovascular disease and type 2 diabetes mellitus were conducted using the variance decomposition approach implemented in SOLAR. A second analysis in unrelated subjects compared these risk factors between sex- and age-matched lean and obese subjects with high and low adiponectin levels. We found significant evidence of pleiotropy (i.e., shared genetic effects) between plasma levels of adiponectin and well-established risk factors for cardiovascular disease and type 2 diabetes mellitus. Individuals with low adiponectin levels per body weight had more adverse risk profiles. These findings offer new insights into the genetic connection between increasing adiposity and risk for cardiovascular disease and type 2 diabetes mellitus, and they suggest that adiponectin may be an important risk factor for the development of these conditions. 相似文献
995.
The intentional introduction of red king crab, Paralithodes camtschatica (Tilesius, 1815) in the Barents Sea represent one of a few successful cases and one that now supports a commercial fishery.
Introductions of alien species into new environments are often associated with genetic bottlenecks, which cause a reduction
in the genetic variation, and this could be important for the spreading potential of the species in the Atlantic Ocean. Red
king crab samples collected in the Varangerfjord located on the Barents Sea (northern Norway) were compared with reference
crab samples collected from the Bering Sea and Kamchatka regions in the Pacific Ocean. All samples were screened for eleven
microsatellite loci, based on the development of species-specific primers. The observed number of alleles per locus was similar,
and no reduction in genetic variation, including gene diversity and allelic richness, was detected between the Varangerfjord
sample and the reference sample from Okhotsk Sea near Kamchatka, indicating no genetic bottlenecking at least for the microsatellite
loci investigated. The same results were found in comparison with the sample from Bering Sea. The level of genetic differentiation
among the samples, measured as overall F
ST
across all loci, was relatively low (0.0238) with a range of 0.0035–0.1000 for the various loci investigated. The largest
pairwise F
ST
values were found between the Bering Sea and Varangerfjord/Barents Sea samples, with a value of 0.0194 across all loci tested.
The lowest value (0.0101) was found between the Varangerfjord and Kamchatka samples. Genetic differentiation based on exact
tests on allele frequencies revealed highly significant differences between all pairwise comparisons. The high level of genetic
variation found in the Varangerfjord/Barents Sea sample could be of significance with respect to further spreading of the
species to other regions in the North Atlantic Ocean. 相似文献
996.
Stein CM Zalwango S Chiunda AB Millard C Leontiev DV Horvath AL Cartier KC Chervenak K Boom WH Elston RC Mugerwa RD Whalen CC Iyengar SK 《Human genetics》2007,121(6):663-673
Tuberculosis (TB) is a growing public health threat globally and several studies suggest a role of host genetic susceptibility
in increased TB risk. As part of a household contact study in Kampala, Uganda, we have taken a unique approach to the study
of genetic susceptibility to TB by developing an intermediate phenotype model for TB susceptibility, analyzing levels of tumor
necrosis factor-α (TNFα) in response to culture filtrate as the phenotype. In the present study, we analyzed candidate genes
related to TNFα regulation and found that interleukin (IL)-10, interferon-gamma receptor 1 (IFNGR1), and TNFα receptor 1 (TNFR1) genes were linked and associated to both TB and TNFα. We also show that these associations are with progression to active
disease and not susceptibility to latent infection. This is the first report of an association between TB and TNFR1 in a human population and our findings for IL-10 and IFNGR1 replicate previous findings. By observing pleiotropic effects on both phenotypes, we show construct validity of our intermediate
phenotype model, which enables the characterization of the role of these genetic polymorphisms on TB pathogenesis. This study
further illustrates the utility of such a model for disentangling complex traits.
C. C. Whalen and S. K. Iyengar contributed equally as senior authors of this work. 相似文献
997.
Liffourrena AS Massimelli MJ Forrellad MA Lisa AT Domenech CE Lucchesi GI 《Current microbiology》2007,55(6):530-536
Pseudomonas aeruginosa expresses hemolytic phospholipase C (PlcH) with choline or under phosphate-limiting conditions. PlcH from these conditions
were differently eluted from the Celite-545 column after application of an ammonium sulfate linear reverse gradient. The PlcH
from supernatants of bacteria grown in the presence of choline was eluted with 30% ammonium sulfate and was more than 85%
inhibited by tetradecyltrimethylammonium. PlcH from supernatants of bacteria grown with succinate and ammonium ions in a low-phosphate
medium was eluted as a peak with 10% of salt and was less than 10% inhibited by tetradecyltrimethylammonium. PlcH from low
phosphate was purified associated with a protein of 17 kDa. This complex was dissociated and separated on a Sephacryl S-200
column with 1% (w/v) sodium dodecyl sulfate. After this dissociation, the resulting protein of 70 kDa, corresponding to PlcH,
was inhibited by tetradecyltrimethylammonium, showing a protection effect of the accompanying protein. RT-PCR analyses showed
that in choline media, the plcH gene was expressed independently of plcR. In low-phosphate medium, the plcH gene was expressed as a plcHR operon. Because plcR encodes for chaperone proteins, this result correlates with the observation that PlcH from supernatants of bacteria grown
in the presence of choline was purified without an accompanying protein. The consequence of the absence of this chaperone
was that tetradecyltrimethylammonium inhibited the PlcH activity. 相似文献
998.
Xiang MA Rybczynski PJ Patel M Chen RH McComsey DF Zhang HC Gunnet JW Look R Wang Y Minor LK Zhong HM Villani FJ Demarest KT Damiano BP Maryanoff BE 《Bioorganic & medicinal chemistry letters》2007,17(23):6623-6628
We have continued to explore spirobenzazepines as vasopressin receptor antagonists to follow up on RWJ-339489 (2), which had advanced into preclinical development. Further structural modifications were pursued to find a suitable backup compound for human clinical studies. Thus, we identified carboxylic acid derivative 3 (RWJ-676070; JNJ-17158063) as a potent, balanced vasopressin V(1a)/V(2) receptor antagonist with favorable properties for clinical development. Compound 3 is currently undergoing human clinical investigation. 相似文献
999.
Ekblom R Saether SA Jacobsson P Fiske P Sahlman T Grahn M Kålås JA Höglund J 《Molecular ecology》2007,16(7):1439-1451
The genes of the major histocompatibility complex (MHC) code for proteins involved in antigen recognition and triggering of the adaptive immune response, and are therefore likely to be under selection from parasites. These selection regimes may vary in space and time. Here we report a strong geographical structure in MHC class II B genes of a migrating bird, the great snipe (Gallinago media). Genetic differentiation in the MHC between two ecologically distinct distributional regions (Scandinavian mountain populations vs. East European lowland populations) was still present after statistically controlling for the effect of selectively neutral variation (microsatellites) using partial Mantel tests. This suggests a role for selection in generating this spatial structure and that it represents local adaptation to different environments. Differentiation between populations within the two regions was negligible. Overall, we found a high number of MHC alleles (50, from 175 individuals). This, together with a tendency for a higher rate of nonsynonymous than synonymous substitutions in the peptide binding sites, and high Tajima's D in certain regions of the gene, suggests a history of balancing selection. MHC variation is often thought to be maintained by some form of balancing selection, but the nature of this selection remains unclear. Our results support the hypothesis that spatial variation in selection regimes contributes to the high polymorphism. 相似文献
1000.
Natural hybridization accompanied by a shift in niche preference by hybrid genotypes can lead to hybrid speciation. Natural selection may cause the fixation of advantageous alleles in the ecologically diverged hybrids, and the loci experiencing selection should exhibit a reduction in allelic diversity relative to neutral loci. Here, we analyzed patterns of genetic diversity at 59 microsatellite loci associated with expressed sequence tags (ESTs) in a homoploid hybrid sunflower species, Helianthus anomalus. We used two indices, ln RV and ln RH, to compare variation and heterozygosity (respectively) at each locus between the hybrid species and its two parental species, H. annuus and H. petiolaris. Mean values of ln RV and ln RH were significantly lower than zero, which implies that H. anomalus experienced a population bottleneck during its recent evolutionary history. After correcting for the apparent bottleneck, we found six loci with a significant reduction in variation or with heterozygosity in the hybrid species, compared to one or both of the parental species. These loci should be viewed as a ranked list of candidate loci, pending further sequencing and functional analyses. Sequence data were generated for two of the candidate loci, but population genetics tests failed to detect deviations from neutral evolution at either locus. Nonetheless, a greater than eight-fold excess of nonsynonymous substitutions was found near a putative N-myristoylation motif at the second locus (HT998), and likelihood-based models indicated that the protein has been under selection in H. anomalus in the past and, perhaps, in one or both parental species. Finally, our data suggest that selective sweeps may have united populations of H. anomalus isolated by a mountain range, indicating that even low gene-flow species may be held together by the spread of advantageous alleles. 相似文献