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21.
James A. Cahill Richard E. Green Tara L. Fulton Mathias Stiller Flora Jay Nikita Ovsyanikov Rauf Salamzade John St. John Ian Stirling Montgomery Slatkin Beth Shapiro 《PLoS genetics》2013,9(3)
Despite extensive genetic analysis, the evolutionary relationship between polar bears (Ursus maritimus) and brown bears (U. arctos) remains unclear. The two most recent comprehensive reports indicate a recent divergence with little subsequent admixture or a much more ancient divergence followed by extensive admixture. At the center of this controversy are the Alaskan ABC Islands brown bears that show evidence of shared ancestry with polar bears. We present an analysis of genome-wide sequence data for seven polar bears, one ABC Islands brown bear, one mainland Alaskan brown bear, and a black bear (U. americanus), plus recently published datasets from other bears. Surprisingly, we find clear evidence for gene flow from polar bears into ABC Islands brown bears but no evidence of gene flow from brown bears into polar bears. Importantly, while polar bears contributed <1% of the autosomal genome of the ABC Islands brown bear, they contributed 6.5% of the X chromosome. The magnitude of sex-biased polar bear ancestry and the clear direction of gene flow suggest a model wherein the enigmatic ABC Island brown bears are the descendants of a polar bear population that was gradually converted into brown bears via male-dominated brown bear admixture. We present a model that reconciles heretofore conflicting genetic observations. We posit that the enigmatic ABC Islands brown bears derive from a population of polar bears likely stranded by the receding ice at the end of the last glacial period. Since then, male brown bear migration onto the island has gradually converted these bears into an admixed population whose phenotype and genotype are principally brown bear, except at mtDNA and X-linked loci. This process of genome erosion and conversion may be a common outcome when climate change or other forces cause a population to become isolated and then overrun by species with which it can hybridize. 相似文献
22.
23.
Kevin D. Shield Gerrit Gmel Tara Kehoe-Chan Deborah A. Dawson Bridget F. Grant Jürgen Rehm 《PloS one》2013,8(1)
Background
Alcohol has been linked to health disparities between races in the US; however, race-specific alcohol-attributable mortality has never been estimated. The objective of this article is to estimate premature mortality attributable to alcohol in the US in 2005, differentiated by race, age and sex for people 15 to 64 years of age.Methods and Findings
Mortality attributable to alcohol was estimated based on alcohol-attributable fractions using indicators of exposure from the National Epidemiologic Survey on Alcohol and Related Conditions and risk relations from the Comparative Risk Assessment study. Consumption data were corrected for undercoverage (the observed underreporting of alcohol consumption when using survey as compared to sales data) using adult per capita consumption from WHO databases. Mortality data by cause of death were obtained from the US Department of Health and Human Services. For people 15 to 64 years of age in the US in 2005, alcohol was responsible for 55,974 deaths (46,461 for men; 9,513 for women) representing 9.0% of all deaths, and 1,288,700 PYLL (1,087,280 for men; 201,420 for women) representing 10.7% of all PYLL. Per 100,000 people, this represents 29 deaths (29 for White; 40 for Black; 82 for Native Americans; 6 for Asian/Pacific Islander) and 670 PYLL (673 for White; 808 for Black; 1,808 for Native American; 158 for Asian/Pacific Islander). Sensitivity analyses showed a lower but still substantial burden without adjusting for undercoverage.Conclusions
The burden of mortality attributable to alcohol in the US is unequal among people of different races and between men and women. Racial differences in alcohol consumption and the resulting harms explain in part the observed disparities in the premature mortality burden between races, suggesting the need for interventions for specific subgroups of the population such as Native Americans. 相似文献24.
Alastair J. King Marc R. Arnone Maureen R. Bleam Katherine G. Moss Jingsong Yang Kelly E. Fedorowicz Kimberly N. Smitheman Joseph A. Erhardt Angela Hughes-Earle Laurie S. Kane-Carson Robert H. Sinnamon Hongwei Qi Tara R. Rheault David E. Uehling Sylvie G. Laquerre 《PloS one》2013,8(7)
Mitogen-Activated Protein Kinase (MAPK) pathway activation has been implicated in many types of human cancer. BRAF mutations that constitutively activate MAPK signalling and bypass the need for upstream stimuli occur with high prevalence in melanoma, colorectal carcinoma, ovarian cancer, papillary thyroid carcinoma, and cholangiocarcinoma. In this report we characterize the novel, potent, and selective BRAF inhibitor, dabrafenib (GSK2118436). Cellular inhibition of BRAFV600E kinase activity by dabrafenib resulted in decreased MEK and ERK phosphorylation and inhibition of cell proliferation through an initial G1 cell cycle arrest, followed by cell death. In a BRAFV600E-containing xenograft model of human melanoma, orally administered dabrafenib inhibited ERK activation, downregulated Ki67, and upregulated p27, leading to tumor growth inhibition. However, as reported for other BRAF inhibitors, dabrafenib also induced MAPK pathway activation in wild-type BRAF cells through CRAF (RAF1) signalling, potentially explaining the squamous cell carcinomas and keratoacanthomas arising in patients treated with BRAF inhibitors. In addressing this issue, we showed that concomitant administration of BRAF and MEK inhibitors abrogated paradoxical BRAF inhibitor-induced MAPK signalling in cells, reduced the occurrence of skin lesions in rats, and enhanced the inhibition of human tumor xenograft growth in mouse models. Taken together, our findings offer preclinical proof of concept for dabrafenib as a specific and highly efficacious BRAF inhibitor and provide evidence for its potential clinical benefits when used in combination with a MEK inhibitor. 相似文献
25.
Mirville Melanie O. Ridley Amanda R. Samedi J. P. M. Vecellio Veronica Ndagijimana Felix Stoinski Tara S. Grueter Cyril C. 《International journal of primatology》2020,41(2):382-400
International Journal of Primatology - Group-living animals face a number of threats from extragroup conspecifics: from individuals seeking mating opportunities to rival groups attempting to access... 相似文献
26.
Bishop Tara B. B. Gill Richard A. McMillan Brock R. St. Clair Samuel B. 《Oecologia》2020,192(1):155-167
Oecologia - Biological invasions are responsive to changing wildfire regimes related to human activities that are altering biological communities. Our objective was to investigate how fire, rodent... 相似文献
27.
Tara Patrick Olga Gonzalez Edward J. Dick Jr. Shyamesh Kumar 《Journal of medical primatology》2020,49(2):110-112
Perosomus Elumbis (PE) is a rare congenital disorder characterized by absence of caudal spine (lumbar, sacral, and coccygeal vertebrae). Here, we present the first reported case of PE in a rhesus macaque (Macaca mulatta) and relate our findings to those described in other species. 相似文献
28.
Genomic sequence duplication is an important mechanism for genome evolution, often resulting in large sequence variations with implications for disease progression. Although paired-end sequencing technologies are commonly used for structural variation discovery, the discovery of novel duplicated sequences remains an unmet challenge. We analyze duplicons starting from identified high-copy number variants. Given paired-end mapped reads, and a candidate high-copy region, our tool, Reprever, identifies (a) the insertion breakpoints where the extra duplicons inserted into the donor genome and (b) the actual sequence of the duplicon. Reprever resolves ambiguous mapping signatures from existing homologs, repetitive elements and sequencing errors to identify breakpoint. At each breakpoint, Reprever reconstructs the inserted sequence using profile hidden Markov model (PHMM)-based guided assembly. In a test on 1000 artificial genomes with simulated duplication, Reprever could identify novel duplicates up to 97% of genomes within 3 bp positional and 1% sequence errors. Validation on 680 fosmid sequences identified and reconstructed eight duplicated sequences with high accuracy. We applied Reprever to reanalyzing a re-sequenced data set from the African individual NA18507 to identify >800 novel duplicates, including insertions in genes and insertions with additional variation. polymerase chain reaction followed by capillary sequencing validated both the insertion locations of the strongest predictions and their predicted sequence. 相似文献
29.
To date, five human metabotropic glutamate (mGlu) 1 receptor splice variants (1a, 1b, 1d, 1f, and 1g) have been described, all of which involve alternative C-terminal splicing. mGlu1a receptor contains a long C-terminal domain (341 amino acids), which has been shown to scaffold with several proteins and contribute to the structure of the post-synaptic density. However, several shorter mGlu1 receptor splice variants lack the sequence required for these interactions, and no major functional differences between these short splice variants have been described. By using RT-PCR we have shown that two human melanoma cell lines express both mGlu1a and mGlu1b receptors. In addition, using 3′RACE, we identified three previously unknown mGlu1 receptor mRNAs. Two differ in the length of their 3′ untranslated region (UTR), and encode the same predicted protein as mGlu1g receptor—the shortest of all mGlu1 receptor splice variants. The third mRNA, named mGlu1h, encodes a predicted C-terminal splice variant of 10 additional amino acids. mGlu1h mRNA was observed in two different melanoma cell lines and is overexpressed, compared with melanoma precursor cells, melanocytes. Most importantly, this new splice variant, mGlu1h receptor, is encoded by two previously unidentified exons located within the human GRM1 gene. Additionally, these new exons are found exclusively within the GRM1 genes of higher primates and are highly conserved. Therefore, we hypothesize that mGlu1h receptors play a distinct role in primate glutamatergic signaling. 相似文献
30.
Tara Kiran Alexander Kopp Rahim Moineddin J. Charles Victor Robert J. Campbell Baiju R. Shah Richard H. Glazier 《CMAJ》2013,185(3):E167-E173