全文获取类型
收费全文 | 3730篇 |
免费 | 110篇 |
国内免费 | 31篇 |
出版年
2023年 | 9篇 |
2022年 | 36篇 |
2021年 | 54篇 |
2020年 | 18篇 |
2019年 | 8篇 |
2018年 | 20篇 |
2017年 | 17篇 |
2016年 | 271篇 |
2015年 | 1020篇 |
2014年 | 1340篇 |
2013年 | 106篇 |
2012年 | 143篇 |
2011年 | 114篇 |
2010年 | 94篇 |
2009年 | 58篇 |
2008年 | 49篇 |
2007年 | 33篇 |
2006年 | 29篇 |
2005年 | 59篇 |
2004年 | 63篇 |
2003年 | 32篇 |
2002年 | 43篇 |
2001年 | 36篇 |
2000年 | 22篇 |
1999年 | 18篇 |
1998年 | 11篇 |
1997年 | 12篇 |
1996年 | 6篇 |
1995年 | 4篇 |
1994年 | 5篇 |
1993年 | 18篇 |
1992年 | 13篇 |
1991年 | 8篇 |
1990年 | 6篇 |
1989年 | 15篇 |
1988年 | 6篇 |
1986年 | 4篇 |
1985年 | 3篇 |
1984年 | 3篇 |
1973年 | 3篇 |
1967年 | 2篇 |
1966年 | 3篇 |
1964年 | 2篇 |
1960年 | 2篇 |
1957年 | 6篇 |
1956年 | 2篇 |
1955年 | 2篇 |
1954年 | 2篇 |
1943年 | 2篇 |
1925年 | 2篇 |
排序方式: 共有3871条查询结果,搜索用时 31 毫秒
81.
82.
83.
84.
Christopher Bryant Kelly S. Giovanello Joseph G. Ibrahim Jing Chang Dinggang Shen Bradley S. Peterson Hongtu Zhu for The Alzheimer's Disease Neuroimaging Initiative 《PloS one》2013,8(8)
Typically twin studies are used to investigate the aggregate effects of genetic and environmental influences on brain phenotypic measures. Although some phenotypic measures are highly heritable in twin studies, SNPs (single nucleotide polymorphisms) identified by genome-wide association studies (GWAS) account for only a small fraction of the heritability of these measures. We mapped the genetic variation (the proportion of phenotypic variance explained by variation among SNPs) of volumes of pre-defined regions across the whole brain, as explained by 512,905 SNPs genotyped on 747 adult participants from the Alzheimer''s Disease Neuroimaging Initiative (ADNI). We found that 85% of the variance of intracranial volume (ICV) (p = 0.04) was explained by considering all SNPs simultaneously, and after adjusting for ICV, total grey matter (GM) and white matter (WM) volumes had genetic variation estimates near zero (p = 0.5). We found varying estimates of genetic variation across 93 non-overlapping regions, with asymmetry in estimates between the left and right cerebral hemispheres. Several regions reported in previous studies to be related to Alzheimer''s disease progression were estimated to have a large proportion of volumetric variance explained by the SNPs. 相似文献
85.
Irene Pichler Fabiola Del Greco M. Martin G?gele Christina M. Lill Lars Bertram Chuong B. Do Nicholas Eriksson Tatiana Foroud Richard H. Myers PD GWAS Consortium Michael Nalls Margaux F. Keller International Parkinson's Disease Genomics Consortium Wellcome Trust Case Control Consortium Beben Benyamin John B. Whitfield Genetics of Iron Status Consortium Peter P. Pramstaller Andrew A. Hicks John R. Thompson Cosetta Minelli 《PLoS medicine》2013,10(6)
Background
Although levels of iron are known to be increased in the brains of patients with Parkinson disease (PD), epidemiological evidence on a possible effect of iron blood levels on PD risk is inconclusive, with effects reported in opposite directions. Epidemiological studies suffer from problems of confounding and reverse causation, and mendelian randomization (MR) represents an alternative approach to provide unconfounded estimates of the effects of biomarkers on disease. We performed a MR study where genes known to modify iron levels were used as instruments to estimate the effect of iron on PD risk, based on estimates of the genetic effects on both iron and PD obtained from the largest sample meta-analyzed to date.Methods and Findings
We used as instrumental variables three genetic variants influencing iron levels, HFE rs1800562, HFE rs1799945, and TMPRSS6 rs855791. Estimates of their effect on serum iron were based on a recent genome-wide meta-analysis of 21,567 individuals, while estimates of their effect on PD risk were obtained through meta-analysis of genome-wide and candidate gene studies with 20,809 PD cases and 88,892 controls. Separate MR estimates of the effect of iron on PD were obtained for each variant and pooled by meta-analysis. We investigated heterogeneity across the three estimates as an indication of possible pleiotropy and found no evidence of it. The combined MR estimate showed a statistically significant protective effect of iron, with a relative risk reduction for PD of 3% (95% CI 1%–6%; p = 0.001) per 10 µg/dl increase in serum iron.Conclusions
Our study suggests that increased iron levels are causally associated with a decreased risk of developing PD. Further studies are needed to understand the pathophysiological mechanism of action of serum iron on PD risk before recommendations can be made. Please see later in the article for the Editors'' Summary 相似文献86.
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
87.
Sophie Garnier Vinh Truong Jessy Brocheton Tanja Zeller Maxime Rovital Philipp S. Wild Andreas Ziegler The Cardiogenics Consortium Thomas Munzel Laurence Tiret Stefan Blankenberg Panos Deloukas Jeannette Erdmann Christian Hengstenberg Nilesh J. Samani Heribert Schunkert Willem H. Ouwehand Alison H. Goodall Fran?ois Cambien David-Alexandre Trégou?t 《PLoS genetics》2013,9(1)
88.
The Can Caesar-TonThat Erin Espeland Anthony J. Caesar Upendra M. Sainju Robert T. Lartey John F. Gaskin 《Microbial ecology》2013,66(1):120-131
Stimulation of plant productivity caused by Agaricus fairy rings has been reported, but little is known about the effects of these fungi on soil aggregation and the microbial community structure, particularly the communities that can bind soil particles. We studied three concentric zones of Agaricus lilaceps fairy rings in Eastern Montana that stimulate western wheatgrass (Pascopyrum smithii): outside the ring (OUT), inside the ring (IN), and stimulated zone adjacent to the fungal fruiting bodies (SZ) to determine (1) soil aggregate proportion and stability, (2) the microbial community composition and the N-acetyl-β-d-glucosaminidase activity associated with bulk soil at 0–15 cm depth, (3) the predominant culturable bacterial communities that can bind to soil adhering to wheatgrass roots, and (4) the stimulation of wheatgrass production. In bulk soil, macroaggregates (4.75–2.00 and 2.00–0.25 mm) and aggregate stability increased in SZ compared to IN and OUT. The high ratio of fungal to bacteria (fatty acid methyl ester) and N-acetyl-β-d-glucosaminidase activity in SZ compared to IN and OUT suggest high fungal biomass. A soil sedimentation assay performed on the predominant isolates from root-adhering soil indicated more soil-binding bacteria in SZ than IN and OUT; Pseudomonas fluorescens and Stenotrophomonas maltophilia isolates predominated in SZ, whereas Bacillus spp. isolates predominated in IN and OUT. This study suggests that growth stimulation of wheatgrass in A. lilaceps fairy rings may be attributed to the activity of the fungus by enhancing soil aggregation of bulk soil at 0–15 cm depth and influencing the amount and functionality of specific predominant microbial communities in the wheatgrass root-adhering soil. 相似文献
89.
Michael?R. Knowles Margaret?W. Leigh Lawrence?E. Ostrowski Lu Huang Johnny?L. Carson Milan?J. Hazucha Weining Yin Jonathan?S. Berg Stephanie?D. Davis Sharon?D. Dell Thomas?W. Ferkol Margaret Rosenfeld Scott?D. Sagel Carlos?E. Milla Kenneth?N. Olivier Emily?H. Turner Alexandra?P. Lewis Michael?J. Bamshad Deborah?A. Nickerson Jay Shendure Maimoona?A. Zariwala the Genetic Disorders of Mucociliary Clearance?Consortium 《American journal of human genetics》2013,92(1):99-106
Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, autosomal-recessive disorder, characterized by oto-sino-pulmonary disease and situs abnormalities. PCD-causing mutations have been identified in 14 genes, but they collectively account for only ∼60% of all PCD. To identify mutations that cause PCD, we performed exome sequencing on six unrelated probands with ciliary outer dynein arm (ODA) defects. Mutations in CCDC114, an ortholog of the Chlamydomonas reinhardtii motility gene DCC2, were identified in a family with two affected siblings. Sanger sequencing of 67 additional individuals with PCD with ODA defects from 58 families revealed CCDC114 mutations in 4 individuals in 3 families. All 6 individuals with CCDC114 mutations had characteristic oto-sino-pulmonary disease, but none had situs abnormalities. In the remaining 5 individuals with PCD who underwent exome sequencing, we identified mutations in two genes (DNAI2, DNAH5) known to cause PCD, including an Ashkenazi Jewish founder mutation in DNAI2. These results revealed that mutations in CCDC114 are a cause of ciliary dysmotility and PCD and further demonstrate the utility of exome sequencing to identify genetic causes in heterogeneous recessive disorders. 相似文献
90.
Elin Grundberg Eshwar Meduri Johanna?K. Sandling ?sa?K. Hedman Sarah Keildson Alfonso Buil Stephan Busche Wei Yuan James Nisbet Magdalena Sekowska Alicja Wilk Amy Barrett Kerrin?S. Small Bing Ge Maxime Caron So-Youn Shin the Multiple Tissue Human Expression Resource Consortium Mark Lathrop Emmanouil T. Dermitzakis Mark I. McCarthy Timothy D. Spector Jordana T. Bell Panos Deloukas 《American journal of human genetics》2013,93(5):876-890
Epigenetic modifications such as DNA methylation play a key role in gene regulation and disease susceptibility. However, little is known about the genome-wide frequency, localization, and function of methylation variation and how it is regulated by genetic and environmental factors. We utilized the Multiple Tissue Human Expression Resource (MuTHER) and generated Illumina 450K adipose methylome data from 648 twins. We found that individual CpGs had low variance and that variability was suppressed in promoters. We noted that DNA methylation variation was highly heritable (h2median = 0.34) and that shared environmental effects correlated with metabolic phenotype-associated CpGs. Analysis of methylation quantitative-trait loci (metQTL) revealed that 28% of CpGs were associated with nearby SNPs, and when overlapping them with adipose expression quantitative-trait loci (eQTL) from the same individuals, we found that 6% of the loci played a role in regulating both gene expression and DNA methylation. These associations were bidirectional, but there were pronounced negative associations for promoter CpGs. Integration of metQTL with adipose reference epigenomes and disease associations revealed significant enrichment of metQTL overlapping metabolic-trait or disease loci in enhancers (the strongest effects were for high-density lipoprotein cholesterol and body mass index [BMI]). We followed up with the BMI SNP rs713586, a cg01884057 metQTL that overlaps an enhancer upstream of ADCY3, and used bisulphite sequencing to refine this region. Our results showed widespread population invariability yet sequence dependence on adipose DNA methylation but that incorporating maps of regulatory elements aid in linking CpG variation to gene regulation and disease risk in a tissue-dependent manner. 相似文献