全文获取类型
收费全文 | 32044篇 |
免费 | 2757篇 |
国内免费 | 2077篇 |
出版年
2024年 | 46篇 |
2023年 | 331篇 |
2022年 | 779篇 |
2021年 | 1437篇 |
2020年 | 931篇 |
2019年 | 1122篇 |
2018年 | 1112篇 |
2017年 | 846篇 |
2016年 | 1222篇 |
2015年 | 1838篇 |
2014年 | 2124篇 |
2013年 | 2339篇 |
2012年 | 2836篇 |
2011年 | 2474篇 |
2010年 | 1570篇 |
2009年 | 1316篇 |
2008年 | 1820篇 |
2007年 | 1538篇 |
2006年 | 1376篇 |
2005年 | 1263篇 |
2004年 | 1082篇 |
2003年 | 992篇 |
2002年 | 878篇 |
2001年 | 565篇 |
2000年 | 427篇 |
1999年 | 514篇 |
1998年 | 359篇 |
1997年 | 293篇 |
1996年 | 320篇 |
1995年 | 269篇 |
1994年 | 315篇 |
1993年 | 217篇 |
1992年 | 268篇 |
1991年 | 234篇 |
1990年 | 216篇 |
1989年 | 155篇 |
1988年 | 130篇 |
1987年 | 124篇 |
1986年 | 98篇 |
1985年 | 120篇 |
1984年 | 89篇 |
1983年 | 84篇 |
1982年 | 91篇 |
1981年 | 80篇 |
1980年 | 62篇 |
1979年 | 59篇 |
1978年 | 43篇 |
1977年 | 48篇 |
1976年 | 44篇 |
1973年 | 38篇 |
排序方式: 共有10000条查询结果,搜索用时 234 毫秒
891.
The molecular mechanism of human anal squamous cell carcinoma (ASCC) is unclear, and the accumulating evidence indicate association of ASCC with the activation of the Akt/mTOR pathway. Here we describe a mouse model with spontaneous anal squamous cell cancer, wherein a combined deletion of Tgfbr1 and Pten in stratified squamous epithelia was induced using inducible K14-Cre. Histopathologic analyses confirmed that 33.3% of the mice showed increased susceptibility to ASCC and precancerous lesions. Biomarker analyses demonstrated that the activation of the Akt pathway in ASCC of the Tgfbr1 and Pten double knockout (2cKO) mouse was similar to that observed in human anal cancer. Chemopreventive experiments using mTOR inhibitor-rapamycin treatment significantly delayed the onset of the ASCC tumors and reduced the tumor burden in 2cKO mice by decreasing the phosphorylation of Akt and S6. This is the first conditional knockout mouse model used for investigating the contributions of viral and cellular factors in anal carcinogenesis without carcinogen-mediated induction, and it would provide a platform for assessing new therapeutic modalities for treating and/or preventing this type of cancer. 相似文献
892.
Yuan-ting Liu Yu-ying Fan Chun-hua Xu Xiao-ling Lin Yun-kai Lu Xing-lan Zhang Cai-xia Zhang Yu-ming Chen 《PloS one》2013,8(10)
Background and Objectives
Many studies have shown a negative association between the consumption of soy products and the risk of some cancers, but little is known about the effect of soy consumption on nasopharyngeal carcinoma. We assessed the association between the consumption of soy products on nasopharyngeal carcinoma risk in Chinese individuals.Methods
This case-control study included 600 (448 males and 152 females) incident cases of nasopharyngeal carcinoma, and an equal number of controls, matched according to gender, age (± 3 y) and household type to the nasopharyngeal carcinoma cases. All subjects were recruited from hospitals in Guangzhou, China. A face-to-face interview was conducted with each study individual to collect general information and habitual dietary intake using a 78-item quantitative food-frequency questionnaire. Odds ratios and their 95% confidence intervals were estimated using conditional logistic regression analyses.Results
The median intakes of soy foods (in protein) were 0.5/0.5, 1.4/1.7, 2.7/3.3 and 6.1/7.7 (male/female) g/d in the quartiles 1 to 4. Both univariate and multivariate analyses showed no significant association between the consumption of soy proteins or soy isoflavones and the risk of nasopharyngeal carcinoma. The adjusted odds ratios (95% confidence intervals) between extreme quartiles were 0.97 (0.66-1.45) for soy proteins and 0.97 (0.66-1.42) for total isoflavones. Null associations were also observed between intake of the individual isoflavones daidzein, genistein and glycitein and NPC risk, with adjusted odds ratios for the extreme quartiles ranging between 0.73 and 1.23.Conclusion
Habitual consumption of soy products had no significant effect on the risk of nasopharyngeal carcinoma in Chinese adults with a relatively low intake. 相似文献893.
Hui-Chun Yu Ming-Chi Lu Chin Li Hsien-Lu Huang Kuang-Yung Huang Su-Qin Liu Ning-Sheng Lai Hsien-Bin Huang 《PloS one》2013,8(10)
The development of suitable methods to deliver peptides specifically to the endoplasmic reticulum (ER) can provide some potential therapeutic applications of such peptides. Ankylosing spondylitis (AS) is strongly associated with the expression of human leukocytic antigen-B27 (HLA-B27). HLA-B27 heavy chain (HC) has a propensity to fold slowly resulting in the accumulation of misfolded HLA-B27 HC in the ER, triggering the unfolded protein response, and forming a homodimer, (B27-HC)2. Natural killer cells and T-helper 17 cells are then activated, contributing to the major pathogenic potentials of AS. The HLA-B27 HC is thus an important target, and delivery of an HLA-B27-binding peptide to the ER capable of promoting HLA-B27 HC folding is a potential mechanism for AS therapy. Here, we demonstrate that a His6-ubiquitin-tagged Tat-derived peptide (THU) can deliver an HLA-B27-binding peptide to the ER promoting HLA-B27 HC folding. The THU-HLA-B27-binding peptide fusion protein crossed the cell membrane to the cytosol through the Tat-derived peptide. The HLA-B27-binding peptide was specifically cleaved from THU by cytosolic ubiquitin C-terminal hydrolases and subsequently transported into the ER by the transporter associated with antigen processing. This approach has potential application in the development of peptide therapy for AS. 相似文献
894.
Chuncheng Lu Miaofei Xu Ying Wang Yufeng Qin Guizhen Du Wei Wu Xiumei Han Chao Ji Yanli Yang Aihua Gu Yankai Xia Ling Song Shoulin Wang Xinru Wang 《PloS one》2013,8(1)
Background
The meiotic program initiation pathway genes (CYP26B1, NANOS1 and STRA8) have been proposed to play key roles in spermatogenesis.Objective
To elucidate the exact role of the genetic variants of the meiosis initiation genes in spermatogenesis, we genotyped the potential functional genetic variants of CYP26B1, NANOS1 and STRA8 genes, and evaluated their effects on spermatogenesis in our study population.Design, Setting, and Participants
In this study, all subjects were volunteers from the affiliated hospitals of Nanjing Medical University between March 2004 and July 2009 (NJMU Infertile Study). Total 719 idiopathic infertile cases were recruited and divided into three groups according to WHO semen parameters: 201 azoospermia patients (no sperm in the ejaculate even after centrifugation), 155 oligozoospermia patients (sperm counts <20×106/ml) and 363 infertility/normozoospermia subjects (sperm counts >20×106/ml). The control group consisted of 383 subjects with normal semen parameters, all of which had fathered at least one child without assisted reproductive technologies.Measurements
Eight single nucleotide polymorphisms (SNPs) in CYP26B1, NANOS1 and STRA8 genes were determined by TaqMan allelic discrimination assay in 719 idiopathic infertile men and 383 healthy controls.Results and Limitations
The genetic variant rs10269148 of STRA8 gene showed higher risk of spermatogenic impairment in the groups of abnormospermia (including azoospermia subgroup and oligozoospermia subgroup) and azoospermia than the controls with odds ratios and 95% confidence intervals of 2.52 (1.29–4.94) and 2.92 (1.41–6.06), respectively (P = 0.006, 0.002 respective). Notably, larger sample size studies and in vivo or in vitro functional studies are needed to substantiate the biological roles of these variants.Conclusions
Our results provided epidemiological evidence supporting the involvement of genetic polymorphisms of the meiotic program initiation genes in modifying the risk of azoospermia and oligozoospermia in a Han-Chinese population. 相似文献895.
Xingxing Cai Jing Fan Zhuxi Jiang Barbara Basso Francesco Sala Alberto Spada Fabrizio Grassi Bao-Rong Lu 《PloS one》2013,8(11)
The characterization of genetic divergence and relationships of a set of germplasm is essential for its efficient applications in crop breeding and understanding of the origin/evolution of crop varieties from a given geographical region. As the largest rice producing country in Europe, Italy holds rice germplasm with abundant genetic diversity. Although Italian rice varieties and the traditional ones in particular have played important roles in rice production and breeding, knowledge concerning the origin and evolution of Italian traditional varieties is still limited. To solve the puzzle of Italian rice origin, we characterized genetic divergence and relationships of 348 rice varieties from Italy and Asia based on the polymorphisms of microsatellite fingerprints. We also included common wild rice O. rufipogon as a reference in the characterization. Results indicated relatively rich genetic diversity (H
e = 0.63-0.65) in Italian rice varieties. Further analyses revealed a close genetic relationship of the Italian traditional varieties with those from northern China, which provides strong genetic evidence for tracing the possible origin of early established rice varieties in Italy. These findings have significant implications for the rice breeding programs, in which appropriate germplasm can be selected from a given region and utilized for transferring unique genetic traits based on its genetic diversity and evolutionary relationships. 相似文献
896.
897.
Camila Satie Savada Moema Cristina Costa de Lima Mário Luís Orsi Fernanda Simões de Almeida 《Zeitschrift fur angewandte Ichthyologie》2020,36(6):825-829
Ten microsatellite loci were developed and described for Pimelodus microstoma, identified in eggs collected from the lower Das Cinzas river. Nine loci were polymorphic, with 02–19 alleles per locus. The observed heterozygosity values were up to 0.898. Five species of the Pimelodidae family were also tested for amplification of loci, among which Pimelodus maculatus was the most successful in the transferability of primers. These loci have proven to be useful for studying the variability and structuring of populations of Pimelodus microstoma. 相似文献
898.
899.
Yang Meifang Wei Ming Wang Chengjian Lu Yu Jin Wanjun Gao Xi Li Cheng Wang Langhong Huang Linjuan Wang Zhongfu 《Glycoconjugate journal》2020,37(2):165-174
Glycoconjugate Journal - The study of carbohydrates requires large amounts of glycans. N-Glycans can be synthesized but generating large quantities of N-glycans with diverse structures remains... 相似文献
900.
Althea A. Archmiller Andrew D. Johnson Jane Nolan Margaret Edwards Lisa H. Elliott Jake M. Ferguson Fabiola Iannarilli Juliana Vélez Kelsey Vitense Douglas H. Johnson John Fieberg 《The Journal of wildlife management》2020,84(5):1012-1017
Scientific progress depends upon the accumulation of empirical knowledge via reproducible methodology. Although reproducibility is a main tenet of the scientific method, recent studies have highlighted widespread failures in adherence to this ideal. The goal of this study was to gauge the level of computational reproducibility, or the ability to obtain the same results using the same data and analytic methods as in the original publication, in the field of wildlife science. We randomly selected 80 papers published in the Journal of Wildlife Management and Wildlife Society Bulletin between 1 June 2016 and 1 June 2018. Of those that were suitable for reproducibility review (n = 74), we attempted to obtain study data from online repositories or directly from authors. Forty-two authors did not respond to our requests, and we were further unable to obtain data from authors of 13 other studies. Of the 19 studies for which we were able to obtain data and complete our analysis, we judged that 13 were mostly or fully reproducible. We conclude that the studies with publicly available data or data shared upon request were largely reproducible, but we remain concerned about the difficulty in obtaining data from recently published papers. We recommend increased data-sharing, data organization and documentation, communication, and training to advance computational reproducibility in the wildlife sciences. © 2020 The Authors. The Journal of Wildlife Management published by Wiley Periodicals, Inc. on behalf of The Wildlife Society. 相似文献