全文获取类型
收费全文 | 117023篇 |
免费 | 2369篇 |
国内免费 | 2814篇 |
出版年
2024年 | 45篇 |
2023年 | 310篇 |
2022年 | 645篇 |
2021年 | 1321篇 |
2020年 | 864篇 |
2019年 | 1054篇 |
2018年 | 12611篇 |
2017年 | 11210篇 |
2016年 | 8348篇 |
2015年 | 2125篇 |
2014年 | 2097篇 |
2013年 | 2212篇 |
2012年 | 6483篇 |
2011年 | 14624篇 |
2010年 | 13106篇 |
2009年 | 9132篇 |
2008年 | 11057篇 |
2007年 | 12413篇 |
2006年 | 1298篇 |
2005年 | 1390篇 |
2004年 | 1691篇 |
2003年 | 1642篇 |
2002年 | 1348篇 |
2001年 | 741篇 |
2000年 | 536篇 |
1999年 | 453篇 |
1998年 | 262篇 |
1997年 | 239篇 |
1996年 | 264篇 |
1995年 | 205篇 |
1994年 | 258篇 |
1993年 | 181篇 |
1992年 | 240篇 |
1991年 | 220篇 |
1990年 | 181篇 |
1989年 | 120篇 |
1988年 | 100篇 |
1987年 | 88篇 |
1986年 | 49篇 |
1985年 | 63篇 |
1984年 | 55篇 |
1983年 | 56篇 |
1982年 | 39篇 |
1981年 | 24篇 |
1979年 | 25篇 |
1975年 | 20篇 |
1972年 | 255篇 |
1971年 | 283篇 |
1965年 | 19篇 |
1962年 | 26篇 |
排序方式: 共有10000条查询结果,搜索用时 46 毫秒
991.
Miaofei Xu Yufeng Qin Jianhua Qu Chuncheng Lu Ying Wang Wei Wu Ling Song Shoulin Wang Feng Chen Hongbing Shen Jiahao Sha Zhibin Hu Yankai Xia Xinru Wang 《PloS one》2013,8(11)
Background
Oligozoospermia is one of the severe forms of idiopathic male infertility. However, its pathology is largely unknown, and few genetic factors have been defined. Our previous genome-wide association study (GWAS) has identified four risk loci for non-obstructive azoospermia (NOA).Objective
To investigate the potentially functional genetic variants (including not only common variants, but also less-common and rare variants) of these loci on spermatogenic impairment, especially oligozoospermia.Design, Setting, and Participants
A total of 784 individuals with oligozoospermia and 592 healthy controls were recruited to this study from March 2004 and January 2011.Measurements
We conducted a two-stage study to explore the association between oligozoospermia and new makers near NOA risk loci. In the first stage, we used next generation sequencing (NGS) in 96 oligozoospermia cases and 96 healthy controls to screen oligozoospermia-susceptible genetic variants. Next, we validated these variants in a large cohort containing 688 cases and 496 controls by SNPscan for high-throughput Single Nucleotide Polymorphism (SNP) genotyping.Results and Limitations
Totally, we observed seven oligozoospermia associated variants (rs3791185 and rs2232015 in PRMT6, rs146039840 and rs11046992 in Sox5, rs1129332 in PEX10, rs3197744 in SIRPA, rs1048055 in SIRPG) in the first stage. In the validation stage, rs3197744 in SIRPA and rs11046992 in Sox5 were associated with increased risk of oligozoospermia with an odds ratio (OR) of 4.62 (P = 0.005, 95%CI 1.58-13.4) and 1.82 (P = 0.005, 95%CI 1.01-1.64), respectively. Further investigation in larger populations and functional characterizations are needed to validate our findings.Conclusions
Our study provides evidence of independent oligozoospermia risk alleles driven by variants in the potentially functional regions of genes discovered by GWAS. Our findings suggest that integrating sequence data with large-scale genotyping will serve as an effective strategy for discovering risk alleles in the future. 相似文献992.
993.
994.
995.
Fang Lu Lulin Huang Chuntao Lei Guiquan Sha Hong Zheng Xiaoqi Liu Jiyun Yang Yi Shi Ying Lin Bo Gong Xianjun Zhu Shi Ma Lifeng Qiao He Lin Jing Cheng Zhenglin Yang 《PloS one》2013,8(11)
Purpose
This study was intended to identify the disease causing genes in a large Chinese family with autosomal dominant retinitis pigmentosa and macular degeneration.Methods
A genome scan analysis was conducted in this family for disease gene preliminary mapping. Snapshot analysis of selected SNPs for two-point LOD score analysis for candidate gene filter. Candidate gene PRPF31 whole exons'' sequencing was executed to identify mutations.Results
A novel nonsense mutation caused by an insertion was found in PRPF31 gene. All the 19 RP patients in 1085 family are carrying this heterozygous nonsense mutation. The nonsense mutation is in PRPF31 gene exon9 at chr19:54629961-54629961, inserting nucleotide “A” that generates the coding protein frame shift from p.307 and early termination at p.322 in the snoRNA binding domain (NOP domain).Conclusion
This report is the first to associate PRPF31 gene''s nonsense mutation and adRP and JMD. Our findings revealed that PRPF31 can lead to different clinical phenotypes in the same family, resulting either in adRP or syndrome of adRP and JMD. We believe our identification of the novel “A” insertion mutation in exon9 at chr19:54629961-54629961 in PRPF31 can provide further genetic evidence for clinical test for adRP and JMD. 相似文献996.
MicroRNA-199a (miRNA-199a) has been shown to have comprehensive functions and behave differently in different systems and diseases. It is encoded by two loci in the human genome, miR-199a-1 in chromosome 19 and miR-199a-2 in chromosome 1. Both loci give rise to the same miRNAs (miR-199a-5p and miR-199a-3p). The cause of the diverse action of the miRNA in different systems is not clear. However, it is likely due to different regulation of the two genomic loci and variable targets of the miRNA in different cells and tissues. Here we studied promoter methylation of miR-199a in testicular germ cell tumors (TGCTs) and glioblastomas (gliomas) and discovered that hypermethylation in TGCTs of both miR-199a-1 and -2 resulted in its reduced expression, while hypomethylation of miR-199a-2 but not -1 in gliomas may be related to its elevated expression. We also identified a common regulator, REST, which preferentially bound to the methylated promoters of both miR-199a-1 and miR-199a-2. The action of miR-199a is dependent on its downstream targets. We identified MAFB as a putative target of miRNA-199a-5p in TGCTs and confirmed that the tumor suppression activity of the microRNA is mediated by its target MAFB. By studying the mechanisms that control the expressions of miR-199a and its various downstream targets, we hope to use miR-199a as a model to understand the complexity of miRNA biology. 相似文献
997.
Zhanfeng Liu Yongbiao Lin Hongfang Lu Mingmao Ding Yaowen Tan Shejin Xu Shenglei Fu 《PloS one》2013,8(10)
Orchard understory represents an important component of the orchards, performing numerous functions related to soil quality, water relations and microclimate, but little attention has been paid on its effect on soil C sequestration. In the face of global climate change, fruit producers also require techniques that increase carbon (C) sequestration in a cost-effective manner. Here we present a case study to compare the effects of understory management (sod culture vs. clean tillage) on soil C sequestration in four subtropical orchards. The results of a 10-year study indicated that the maintenance of sod significantly enhanced the soil C stock in the top 1 m of orchard soils. Relative to clean tillage, sod culture increased annual soil C sequestration by 2.85 t C ha-1, suggesting that understory management based on sod culture offers promising potential for soil carbon sequestration. Considering that China has the largest area of orchards in the world and that few of these orchards currently have sod understories, the establishment and maintenance of sod in orchards can help China increase C sequestration and greatly contribute to achieving CO2 reduction targets at a regional scale and potentially at a national scale. 相似文献
998.
A p21-activated kinase 6 (PAK6) was previously identified to be an androgen receptor (AR) interacting protein through a yeast two-hybrid screening. We used hormone responsive prostate cancer LAPC4 and LNCap cell lines as models to study the signaling events associated with androgen stimulation and PAK6. An androgen-stimulated PAK6 kinase activation was observed in LAPC4 cells expressing endogenous PAK6 and in LNCap cells ectopically expressing a wild type PAK6. This activation was likely mediated through a direct interaction between AR and PAK6 since siRNA knock-down of AR in LAPC4 cells downregulated androgen-stimulated PAK6 activation. In addition, LNCap cells expressing a non-AR-interacting PAK6 mutant exhibited dampened androgen-stimulated kinase activation. As a consequence of androgen-stimulated activation, PAK6 was phosphorylated at multiple serine/threonine residues including the AR-interacting domain of PAK6. Furthermore, androgen-stimulation promoted prostate cancer cell motility and invasion were demonstrated in LNCap cells ectopically expressing PAK6-WT. In contrast, LNCap expressing non-AR-interacting mutant PAK6 did not respond to androgen stimulation with increased cell motility and invasion. Our results demonstrate that androgen-stimulated PAK6 activation is mediated through a direct interaction between AR and PAK6 and PAK6 activation promotes prostate cancer cells motility and invasion. 相似文献
999.
Wen-Jie Ji Yong-Qiang Ma Xin Zhou Yi-Dan Zhang Rui-Yi Lu Zhao-Zeng Guo Hai-Ying Sun Dao-Chuan Hu Guo-Hong Yang Yu-Ming Li Lu-Qing Wei 《PloS one》2013,8(11)
Background
Recent experimental studies provide evidence indicating that manipulation of the mononuclear phagocyte phenotype could be a feasible approach to alter the severity and persistence of pulmonary injury and fibrosis. Mineralocorticoid receptor (MR) has been reported as a target to regulate macrophage polarization. The present work was designed to investigate the therapeutic potential of MR antagonism in bleomycin-induced acute lung injury and fibrosis.Methodology/Principal Findings
We first demonstrated the expression of MR in magnetic bead-purified Ly6G-/CD11b+ circulating monocytes and in alveolar macrophages harvested in bronchoalveolar lavage fluid (BALF) from C57BL/6 mice. Then, a pharmacological intervention study using spironolactone (20mg/kg/day by oral gavage) revealed that MR antagonism led to decreased inflammatory cell infiltration, cytokine production (downregulated monocyte chemoattractant protein-1, transforming growth factor β1, and interleukin-1β at mRNA and protein levels) and collagen deposition (decreased lung total hydroxyproline content and collagen positive area by Masson’ trichrome staining) in bleomycin treated (2.5mg/kg, via oropharyngeal instillation) male C57BL/6 mice. Moreover, serial flow cytometry analysis in blood, BALF and enzymatically digested lung tissue, revealed that spironolactone could partially inhibit bleomycin-induced circulating Ly6Chi monocyte expansion, and reduce alternative activation (F4/80+CD11c+CD206+) of mononuclear phagocyte in alveoli, whereas the phenotype of interstitial macrophage (F4/80+CD11c-) remained unaffected by spironolactone during investigation.Conclusions/Significance
The present work provides the experimental evidence that spironolactone could attenuate bleomycin-induced acute pulmonary injury and fibrosis, partially via inhibition of MR-mediated circulating monocyte and alveolar macrophage phenotype switching. 相似文献1000.
Min Xia Daxin Chen Valeria Endresz Ildiko Faludi Andrea Szabo Eva Gonczol Vijay Kakkar Xinjie Lu 《PloS one》2013,8(12)