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21.
22.
Simon Gravel Fouad Zakharia Andres Moreno-Estrada Jake K. Byrnes Marina Muzzio Juan L. Rodriguez-Flores Eimear E. Kenny Christopher R. Gignoux Brian K. Maples Wilfried Guiblet Julie Dutil Marc Via Karla Sandoval Gabriel Bedoya The Genomes Project Taras K. Oleksyk Andres Ruiz-Linares Esteban G. Burchard Juan Carlos Martinez-Cruzado Carlos D. Bustamante 《PLoS genetics》2013,9(12)
There is great scientific and popular interest in understanding the genetic history of populations in the Americas. We wish to understand when different regions of the continent were inhabited, where settlers came from, and how current inhabitants relate genetically to earlier populations. Recent studies unraveled parts of the genetic history of the continent using genotyping arrays and uniparental markers. The 1000 Genomes Project provides a unique opportunity for improving our understanding of population genetic history by providing over a hundred sequenced low coverage genomes and exomes from Colombian (CLM), Mexican-American (MXL), and Puerto Rican (PUR) populations. Here, we explore the genomic contributions of African, European, and especially Native American ancestry to these populations. Estimated Native American ancestry is in MXL, in CLM, and in PUR. Native American ancestry in PUR is most closely related to populations surrounding the Orinoco River basin, confirming the Southern America ancestry of the Taíno people of the Caribbean. We present new methods to estimate the allele frequencies in the Native American fraction of the populations, and model their distribution using a demographic model for three ancestral Native American populations. These ancestral populations likely split in close succession: the most likely scenario, based on a peopling of the Americas thousand years ago (kya), supports that the MXL Ancestors split kya, with a subsequent split of the ancestors to CLM and PUR kya. The model also features effective populations of in Mexico, in Colombia, and in Puerto Rico. Modeling Identity-by-descent (IBD) and ancestry tract length, we show that post-contact populations also differ markedly in their effective sizes and migration patterns, with Puerto Rico showing the smallest effective size and the earlier migration from Europe. Finally, we compare IBD and ancestry assignments to find evidence for relatedness among European founders to the three populations. 相似文献
23.
Andrés Moreno-Estrada Simon Gravel Fouad Zakharia Jacob L. McCauley Jake K. Byrnes Christopher R. Gignoux Patricia A. Ortiz-Tello Ricardo J. Martínez Dale J. Hedges Richard W. Morris Celeste Eng Karla Sandoval Suehelay Acevedo-Acevedo Paul J. Norman Zulay Layrisse Peter Parham Juan Carlos Martínez-Cruzado Esteban González Burchard Michael L. Cuccaro Eden R. Martin Carlos D. Bustamante 《PLoS genetics》2013,9(11)
The Caribbean basin is home to some of the most complex interactions in recent history among previously diverged human populations. Here, we investigate the population genetic history of this region by characterizing patterns of genome-wide variation among 330 individuals from three of the Greater Antilles (Cuba, Puerto Rico, Hispaniola), two mainland (Honduras, Colombia), and three Native South American (Yukpa, Bari, and Warao) populations. We combine these data with a unique database of genomic variation in over 3,000 individuals from diverse European, African, and Native American populations. We use local ancestry inference and tract length distributions to test different demographic scenarios for the pre- and post-colonial history of the region. We develop a novel ancestry-specific PCA (ASPCA) method to reconstruct the sub-continental origin of Native American, European, and African haplotypes from admixed genomes. We find that the most likely source of the indigenous ancestry in Caribbean islanders is a Native South American component shared among inland Amazonian tribes, Central America, and the Yucatan peninsula, suggesting extensive gene flow across the Caribbean in pre-Columbian times. We find evidence of two pulses of African migration. The first pulse—which today is reflected by shorter, older ancestry tracts—consists of a genetic component more similar to coastal West African regions involved in early stages of the trans-Atlantic slave trade. The second pulse—reflected by longer, younger tracts—is more similar to present-day West-Central African populations, supporting historical records of later transatlantic deportation. Surprisingly, we also identify a Latino-specific European component that has significantly diverged from its parental Iberian source populations, presumably as a result of small European founder population size. We demonstrate that the ancestral components in admixed genomes can be traced back to distinct sub-continental source populations with far greater resolution than previously thought, even when limited pre-Columbian Caribbean haplotypes have survived. 相似文献
24.
25.
Background
The number of patients seeking health care is a central indicator that may serve several different purposes: (1) as a proxy for the impact on the burden of the primary care system; (2) as a starting point to estimate the number of persons ill with influenza; (3) as the denominator data for the calculation of case fatality rate and the proportion hospitalized (severity indicators); (4) for economic calculations. In addition, reliable estimates of burden of disease and on the health care system are essential to communicate the impact of influenza to health care professionals, public health professionals and to the public.Methodology/Principal Findings
Using German syndromic surveillance data, we have developed a novel approach to describe the seasonal variation of medically attended acute respiratory infections (MAARI) and estimate the excess MAARI attributable to influenza. The weekly excess inside a period of influenza circulation is estimated as the difference between the actual MAARI and a MAARI-baseline, which is established using a cyclic regression model for counts. As a result, we estimated the highest ARI burden within the last 10 years for the influenza season 2004/05 with an excess of 7.5 million outpatient visits (CI95% 6.8–8.0). In contrast, the pandemic wave 2009 accounted for one third of this burden with an excess of 2.4 million (CI95% 1.9–2.8). Estimates can be produced for different age groups, different geographic regions in Germany and also in real time during the influenza waves. 相似文献26.
27.
Meredith?L. Carpenter Jason?D. Buenrostro Cristina Valdiosera Hannes Schroeder Morten?E. Allentoft Martin Sikora Morten Rasmussen Simon Gravel Sonia Guillén Georgi Nekhrizov Krasimir Leshtakov Diana Dimitrova Nikola Theodossiev Davide Pettener Donata Luiselli Karla Sandoval Andrés Moreno-Estrada Yingrui Li Jun Wang M.?Thomas?P. Gilbert Eske Willerslev William?J. Greenleaf Carlos?D. Bustamante 《American journal of human genetics》2013,93(5):852-864
Most ancient specimens contain very low levels of endogenous DNA, precluding the shotgun sequencing of many interesting samples because of cost. Ancient DNA (aDNA) libraries often contain <1% endogenous DNA, with the majority of sequencing capacity taken up by environmental DNA. Here we present a capture-based method for enriching the endogenous component of aDNA sequencing libraries. By using biotinylated RNA baits transcribed from genomic DNA libraries, we are able to capture DNA fragments from across the human genome. We demonstrate this method on libraries created from four Iron Age and Bronze Age human teeth from Bulgaria, as well as bone samples from seven Peruvian mummies and a Bronze Age hair sample from Denmark. Prior to capture, shotgun sequencing of these libraries yielded an average of 1.2% of reads mapping to the human genome (including duplicates). After capture, this fraction increased substantially, with up to 59% of reads mapped to human and enrichment ranging from 6- to 159-fold. Furthermore, we maintained coverage of the majority of regions sequenced in the precapture library. Intersection with the 1000 Genomes Project reference panel yielded an average of 50,723 SNPs (range 3,062–147,243) for the postcapture libraries sequenced with 1 million reads, compared with 13,280 SNPs (range 217–73,266) for the precapture libraries, increasing resolution in population genetic analyses. Our whole-genome capture approach makes it less costly to sequence aDNA from specimens containing very low levels of endogenous DNA, enabling the analysis of larger numbers of samples. 相似文献
28.
Morteza Bashash Amil Shah Greg Hislop Martin Treml Karla Bretherick Rozmin Janoo-Gilani Stephen Leach Nhu Le Chris Bajdik Angela Brooks-Wilson 《PloS one》2013,8(3)
The poor survival of adenocarcinomas of the gastroesophageal junction (GEJ) makes them clinically important. Discovery of host genetic factors that affect outcome may guide more individualized treatment. This study tests whether constitutional genetic variants in matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) genes are associated with outcome of GEJ adenocarcinoma. Single nucleotide polymorphisms (SNPs) at four TIMP (TIMP1-4) and three MMP genes (MMP2, MMP7 and MMP9) were genotyped in DNA samples from a prospective cohort of patients with primary adenocarcinoma of the GEJ admitted to the British Columbia Cancer Agency. Cox proportional hazards regression, with adjustment for patient, disease and treatment variables, was used to estimate the association of SNPs with survival. Genotypes for 85 samples and 48 SNPs were analyzed. Four SNPs across TIMP3, (rs130274, rs715572, rs1962223 and rs5754312) were associated with survival. Interaction analyses revealed that the survival associations with rs715572 and rs5754312 are specific and significant for 5FU+cisplatin treated patients. Sanger sequencing of the TIMP3 coding and promoter regions revealed an additional SNP, rs9862, also associated with survival. TIMP3 genetic variants are associated with survival and may be potentially useful in optimizing treatment strategies for individual patients. 相似文献
29.
Riccardo Papa Durrell D. Kapan Brian A. Counterman Karla Maldonado Daniel P. Lindstrom Robert D. Reed H. Frederik Nijhout Tomas Hrbek W. Owen McMillan 《PloS one》2013,8(3)
Recent studies indicate that relatively few genomic regions are repeatedly involved in the evolution of Heliconius butterfly wing patterns. Although this work demonstrates a number of cases where homologous loci underlie both convergent and divergent wing pattern change among different Heliconius species, it is still unclear exactly how many loci underlie pattern variation across the genus. To address this question for Heliconius erato, we created fifteen independent crosses utilizing the four most distinct color pattern races and analyzed color pattern segregation across a total of 1271 F2 and backcross offspring. Additionally, we used the most variable brood, an F2 cross between H. himera and the east Ecuadorian H. erato notabilis, to perform a quantitative genetic analysis of color pattern variation and produce a detailed map of the loci likely involved in the H. erato color pattern radiation. Using AFLP and gene based markers, we show that fewer major genes than previously envisioned control the color pattern variation in H. erato. We describe for the first time the genetic architecture of H. erato wing color pattern by assessing quantitative variation in addition to traditional linkage mapping. In particular, our data suggest three genomic intervals modulate the bulk of the observed variation in color. Furthermore, we also identify several modifier loci of moderate effect size that contribute to the quantitative wing pattern variation. Our results are consistent with the two-step model for the evolution of mimetic wing patterns in Heliconius and support a growing body of empirical data demonstrating the importance of major effect loci in adaptive change. 相似文献
30.
Nicotine is the main tobacco component responsible for tobacco addiction and is used extensively in smoking and smoking cessation therapies. However, little is known about its effects on the immune system. We confirmed that multiple nicotinic receptors are expressed on mouse and human cytotoxic T lymphocytes (CTLs) and demonstrated that nicotinic receptors on mouse CTLs are regulated during activation. Acute nicotine presence during activation increases primary CTL expansion in vitro, but impairs in vivo expansion after transfer and subsequent memory CTL differentiation, which reduces protection against subsequent pathogen challenges. Furthermore, nicotine abolishes the regulatory effect of rapamycin on memory CTL programming, which can be attributed to the fact that rapamycin enhances expression of nicotinic receptors. Interestingly, naïve CTLs from chronic nicotine-treated mice have normal memory programming, which is impaired by nicotine during activation in vitro. In conclusion, simultaneous exposure to nicotine and antigen during CTL activation negatively affects memory development. 相似文献