全文获取类型
收费全文 | 4380篇 |
免费 | 291篇 |
国内免费 | 4篇 |
出版年
2023年 | 23篇 |
2022年 | 81篇 |
2021年 | 164篇 |
2020年 | 67篇 |
2019年 | 73篇 |
2018年 | 106篇 |
2017年 | 84篇 |
2016年 | 132篇 |
2015年 | 189篇 |
2014年 | 225篇 |
2013年 | 296篇 |
2012年 | 329篇 |
2011年 | 374篇 |
2010年 | 214篇 |
2009年 | 144篇 |
2008年 | 222篇 |
2007年 | 192篇 |
2006年 | 175篇 |
2005年 | 144篇 |
2004年 | 154篇 |
2003年 | 128篇 |
2002年 | 108篇 |
2001年 | 89篇 |
2000年 | 66篇 |
1999年 | 80篇 |
1998年 | 33篇 |
1997年 | 19篇 |
1995年 | 28篇 |
1994年 | 18篇 |
1993年 | 24篇 |
1992年 | 37篇 |
1991年 | 51篇 |
1990年 | 29篇 |
1989年 | 38篇 |
1988年 | 31篇 |
1987年 | 38篇 |
1986年 | 31篇 |
1985年 | 25篇 |
1984年 | 25篇 |
1983年 | 24篇 |
1982年 | 24篇 |
1980年 | 20篇 |
1979年 | 38篇 |
1978年 | 19篇 |
1977年 | 23篇 |
1974年 | 24篇 |
1973年 | 22篇 |
1972年 | 21篇 |
1970年 | 17篇 |
1967年 | 17篇 |
排序方式: 共有4675条查询结果,搜索用时 31 毫秒
141.
MeiHwa Tanielle Bench Alvarez Dipti Jigar Shah Craig D. Thulin Steven W. Graves 《Proteomics》2013,13(9):1400-1411
Analysis of the protein/peptide composition of tissue has provided meaningful insights into tissue biology and even disease mechanisms. However, little has been published regarding top down methods to investigate lower molecular weight (MW) (500–5000 Da) species in tissue. Here, we evaluate a tissue proteomics approach involving tissue homogenization followed by depletion of large proteins and then cLC‐MS (where c stands for capillary) analysis to interrogate the low MW/low abundance tissue proteome. In the development of this method, sheep heart, lung, liver, kidney, and spleen were surveyed to test our ability to observe tissue differences. After categorical tissue differences were demonstrated, a detailed study of this method's reproducibility was undertaken to determine whether or not it is suitable for analyzing more subtle differences in the abundance of small proteins and peptides. Our results suggest that this method should be useful in exploring the low MW proteome of tissues. 相似文献
142.
目的:胰腺癌恶性程度高、进展快、预后差,姜黄素对于抑制恶性肿瘤的发生和进程具有广泛的生物学效应。但姜黄素能否诱导人胰腺癌细胞凋亡,其具体作用机制如何?目前仍无报道。本研究拟观察姜黄素对人胰腺癌PANC.1细胞凋亡的影响,探讨姜黄素诱导PANC.1细胞凋亡的机制。方法:不同浓度姜黄素处理人胰腺癌PANC-1细胞,流式细胞仪检测PANC-1细胞凋亡率,并分析Caspase-9和Caspase-3活性的变化,同时通过RT—PCR和Westemblot分析PANC-1细胞中P53表达的变化。结果:PANC-1细胞经不同浓度的姜黄素处理后,可以显著诱导细胞凋亡,并呈现一定的剂量依赖性,提示姜黄素具有一定抗肿瘤活性。姜黄素能够同时增加Caspase-9和Caspase-3的活性,并呈现一定的剂量依赖性,提示姜黄素可能通过Caspase-9和Caspase-3途径来诱导PANC.1细胞凋亡的发生。RT—PCR和westernblot结果显示,姜黄素可以显著增加PANC-1细胞中P53蛋白表达水平。结论:姜黄素可以显著诱导PANC-1细胞凋亡的发生,提高Caspase-9和Caspase-3的活性,同时增加的P53表达,并呈现一定的剂量依赖性,提示姜黄素诱导PANC-1细胞凋亡的过程可能与增加细胞中Caspase-9,Caspase-3以及P53的表达有关。本研究探讨了姜黄素诱导PANC-1细胞凋亡的分子机制,为姜黄素的进一步应用提供了新的思路和理论支持,在人胰腺癌的临床治疗中具有一定的潜在应用价值。 相似文献
143.
Denice S. Feig Baiju R. Shah Lorraine L. Lipscombe C. Fangyun Wu Joel G. Ray Julia Lowe Jeremiah Hwee Gillian L. Booth 《PLoS medicine》2013,10(4)
Background
Women with preeclampsia (PEC) and gestational hypertension (GH) exhibit insulin resistance during pregnancy, independent of obesity and glucose intolerance. Our aim was to determine whether women with PEC or GH during pregnancy have an increased risk of developing diabetes after pregnancy, and whether the presence of PEC/GH in addition to gestational diabetes (GDM) increases the risk of future (postpartum) diabetes.Methods and Findings
We performed a population-based, retrospective cohort study for 1,010,068 pregnant women who delivered in Ontario, Canada between April 1994 and March 2008. Women were categorized as having PEC alone (n = 22,933), GH alone (n = 27,605), GDM alone (n = 30,852), GDM+PEC (n = 1,476), GDM+GH (n = 2,100), or none of these conditions (n = 925,102). Our main outcome was a new diagnosis of diabetes postpartum in the following years, up until March 2011, based on new records in the Ontario Diabetes Database. The incidence rate of diabetes per 1,000 person-years was 6.47 for women with PEC and 5.26 for GH compared with 2.81 in women with neither of these conditions. In the multivariable analysis, both PEC alone (hazard ratio [HR] = 2.08; 95% CI 1.97–2.19) and GH alone (HR = 1.95; 95% CI 1.83–2.07) were risk factors for subsequent diabetes. Women with GDM alone were at elevated risk of developing diabetes postpartum (HR = 12.77; 95% CI 12.44–13.10); however, the co–presence of PEC or GH in addition to GDM further elevated this risk (HR = 15.75; 95% CI 14.52–17.07, and HR = 18.49; 95% CI 17.12–19.96, respectively). Data on obesity were not available.Conclusions
Women with PEC/GH have a 2-fold increased risk of developing diabetes when followed up to 16.5 years after pregnancy, even in the absence of GDM. The presence of PEC/GH in the setting of GDM also raised the risk of diabetes significantly beyond that seen with GDM alone. A history of PEC/GH during pregnancy should alert clinicians to the need for preventative counseling and more vigilant screening for diabetes. Please see later in the article for the Editors'' Summary 相似文献144.
Caiyong Chen Daniel Garcia-Santos Yuichi Ishikawa Alexandra Seguin Liangtao Li Katherine H. Fegan Gordon J. Hildick-Smith Dhvanit I. Shah Jeffrey D. Cooney Wen Chen Matthew J. King Yvette Y. Yien Iman J. Schultz Heidi Anderson Arthur J. Dalton Matthew L. Freedman Paul D. Kingsley James Palis Barry H. Paw 《Cell metabolism》2013,17(3):343-352
- Download : Download high-res image (201KB)
- Download : Download full-size image
145.
Christopher Millett Sutapa Agrawal Ruth Sullivan Mario Vaz Anura Kurpad A. V. Bharathi Dorairaj Prabhakaran Kolli Srinath Reddy Sanjay Kinra George Davey Smith Shah Ebrahim for the Indian Migration Study group 《PLoS medicine》2013,10(6)
Background
Increasing active travel (walking, bicycling, and public transport) is promoted as a key strategy to increase physical activity and reduce the growing burden of noncommunicable diseases (NCDs) globally. Little is known about patterns of active travel or associated cardiovascular health benefits in low- and middle-income countries. This study examines mode and duration of travel to work in rural and urban India and associations between active travel and overweight, hypertension, and diabetes.Methods and Findings
Cross-sectional study of 3,902 participants (1,366 rural, 2,536 urban) in the Indian Migration Study. Associations between mode and duration of active travel and cardiovascular risk factors were assessed using random-effect logistic regression models adjusting for age, sex, caste, standard of living, occupation, factory location, leisure time physical activity, daily fat intake, smoking status, and alcohol use. Rural dwellers were significantly more likely to bicycle (68.3% versus 15.9%; p<0.001) to work than urban dwellers. The prevalence of overweight or obesity was 50.0%, 37.6%, 24.2%, 24.9%; hypertension was 17.7%, 11.8%, 6.5%, 9.8%; and diabetes was 10.8%, 7.4%, 3.8%, 7.3% in participants who travelled to work by private transport, public transport, bicycling, and walking, respectively. In the adjusted analysis, those walking (adjusted risk ratio [ARR] 0.72; 95% CI 0.58–0.88) or bicycling to work (ARR 0.66; 95% CI 0.55–0.77) were significantly less likely to be overweight or obese than those travelling by private transport. Those bicycling to work were significantly less likely to have hypertension (ARR 0.51; 95% CI 0.36–0.71) or diabetes (ARR 0.65; 95% CI 0.44–0.95). There was evidence of a dose-response relationship between duration of bicycling to work and being overweight, having hypertension or diabetes. The main limitation of the study is the cross-sectional design, which limits causal inference for the associations found.Conclusions
Walking and bicycling to work was associated with reduced cardiovascular risk in the Indian population. Efforts to increase active travel in urban areas and halt declines in rural areas should be integral to strategies to maintain healthy weight and prevent NCDs in India. Please see later in the article for the Editors'' Summary 相似文献146.
147.
148.
Wouter L. W. Hazenbos Kimberly K. Kajihara Richard Vandlen J. Hiroshi Morisaki Sophie M. Lehar Mark J. Kwakkenbos Tim Beaumont Arjen Q. Bakker Qui Phung Lee R. Swem Satish Ramakrishnan Janice Kim Min Xu Ishita M. Shah Binh An Diep Tao Sai Andrew Sebrell Yana Khalfin Angela Oh Chris Koth S. Jack Lin Byoung-Chul Lee Magnus Strandh Klaus Koefoed Peter S. Andersen Hergen Spits Eric J. Brown Man-Wah Tan Sanjeev Mariathasan 《PLoS pathogens》2013,9(10)
Infection of host tissues by Staphylococcus aureus and S. epidermidis requires an unusual family of staphylococcal adhesive proteins that contain long stretches of serine-aspartate dipeptide-repeats (SDR). The prototype member of this family is clumping factor A (ClfA), a key virulence factor that mediates adhesion to host tissues by binding to extracellular matrix proteins such as fibrinogen. However, the biological siginificance of the SDR-domain and its implication for pathogenesis remain poorly understood. Here, we identified two novel bacterial glycosyltransferases, SdgA and SdgB, which modify all SDR-proteins in these two bacterial species. Genetic and biochemical data demonstrated that these two glycosyltransferases directly bind and covalently link N-acetylglucosamine (GlcNAc) moieties to the SDR-domain in a step-wise manner, with SdgB appending the sugar residues proximal to the target Ser-Asp repeats, followed by additional modification by SdgA. GlcNAc-modification of SDR-proteins by SdgB creates an immunodominant epitope for highly opsonic human antibodies, which represent up to 1% of total human IgG. Deletion of these glycosyltransferases renders SDR-proteins vulnerable to proteolysis by human neutrophil-derived cathepsin G. Thus, SdgA and SdgB glycosylate staphylococcal SDR-proteins, which protects them against host proteolytic activity, and yet generates major eptopes for the human anti-staphylococcal antibody response, which may represent an ongoing competition between host and pathogen. 相似文献
149.
Tomohiro Nishimura Shinya Sato Wittaya Tawong Hiroshi Sakanari Keita Uehara Md Mahfuzur Rahman Shah Shoichiro Suda Takeshi Yasumoto Yohsuke Taira Haruo Yamaguchi Masao Adachi 《PloS one》2013,8(4)
Background
The marine epiphytic dinoflagellate genus Gambierdiscus produce toxins that cause ciguatera fish poisoning (CFP): one of the most significant seafood-borne illnesses associated with fish consumption worldwide. So far, occurrences of CFP incidents in Japan have been mainly reported in subtropical areas. A previous phylogeographic study of Japanese Gambierdiscus revealed the existence of two distinct phylotypes: Gambierdiscus sp. type 1 from subtropical and Gambierdiscus sp. type 2 from temperate areas. However, details of the genetic diversity and distribution for Japanese Gambierdiscus are still unclear, because a comprehensive investigation has not been conducted yet.Methods/Principal Finding
A total of 248 strains were examined from samples mainly collected from western and southern coastal areas of Japan during 2006–2011. The SSU rDNA, the LSU rDNA D8–D10 and the ITS region were selected as genetic markers and phylogenetic analyses were conducted. The genetic diversity of Japanese Gambierdiscus was high since five species/phylotypes were detected: including two reported phylotypes (Gambierdiscus sp. type 1 and Gambierdiscus sp. type 2), two species of Gambierdiscus (G. australes and G. cf. yasumotoi) and a hitherto unreported phylotype Gambierdiscus sp. type 3. The distributions of type 3 and G. cf. yasumotoi were restricted to the temperate and the subtropical area, respectively. On the other hand, type 1, type 2 and G. australes occurred from the subtropical to the temperate area, with a tendency that type 1 and G. australes were dominant in the subtropical area, whereas type 2 was dominant in the temperate area. By using mouse bioassay, type 1, type 3 and G. australes exhibited mouse toxicities.Conclusions/Significance
This study revealed a surprising diversity of Japanese Gambierdiscus and the distribution of five species/phylotypes displayed clear geographical patterns in Japanese coastal areas. The SSU rDNA and the LSU rDNA D8–D10 as genetic markers are recommended for further use. 相似文献150.
<i>Aspergillus tubingensis</i> Causes Leaf Spot of Cotton (<i>Gossypium hirsutum</i> L.) in Pakistan
Maria Khizar Urooj Haroon Musrat Ali Samiah Arif Iftikhar Hussain Shah Hassan Javed Chaudhary Muhammad Farooq Hussain Munis 《Phyton》2020,89(1):103-109
Cotton (Gossypium hirsutum L.) is a key fiber crop of great commercial
importance. Numerous phytopathogens decimate crop production by causing
various diseases. During July-August 2018, leaf spot symptoms were recurrently
observed on cotton leaves in Rahim Yar Khan, Pakistan and adjacent areas. Infected
leaf samples were collected and plated on potato dextrose agar (PDA) media.
Causal agent of cotton leaf spot was isolated, characterized and identified as
Aspergillus tubingensis based on morphological and microscopic observations.
Conclusive identification of pathogen was done on the comparative molecular
analysis of CaM and β-tubulin gene sequences. BLAST analysis of both sequenced
genes showed 99% similarity with A. tubingensis. Koch’s postulates were followed
to confirm the pathogenicity of the isolated fungus. Healthy plants were inoculated
with fungus and similar disease symptoms were observed. Fungus was re-isolated
and identified to be identical to the inoculated fungus. To our knowledge, this is the
first report describing the involvement of A. tubingensis in causing leaf spot disease
of cotton in Pakistan and around the world. 相似文献