全文获取类型
收费全文 | 4061篇 |
免费 | 381篇 |
国内免费 | 3篇 |
专业分类
4445篇 |
出版年
2023年 | 30篇 |
2022年 | 60篇 |
2021年 | 132篇 |
2020年 | 79篇 |
2019年 | 92篇 |
2018年 | 115篇 |
2017年 | 106篇 |
2016年 | 171篇 |
2015年 | 309篇 |
2014年 | 277篇 |
2013年 | 271篇 |
2012年 | 445篇 |
2011年 | 359篇 |
2010年 | 230篇 |
2009年 | 188篇 |
2008年 | 269篇 |
2007年 | 240篇 |
2006年 | 197篇 |
2005年 | 191篇 |
2004年 | 134篇 |
2003年 | 130篇 |
2002年 | 108篇 |
2001年 | 18篇 |
2000年 | 20篇 |
1999年 | 12篇 |
1998年 | 29篇 |
1997年 | 9篇 |
1996年 | 8篇 |
1995年 | 12篇 |
1994年 | 12篇 |
1993年 | 12篇 |
1992年 | 16篇 |
1991年 | 13篇 |
1990年 | 9篇 |
1988年 | 12篇 |
1987年 | 5篇 |
1985年 | 5篇 |
1984年 | 14篇 |
1983年 | 8篇 |
1982年 | 6篇 |
1981年 | 9篇 |
1980年 | 7篇 |
1979年 | 8篇 |
1978年 | 6篇 |
1976年 | 4篇 |
1975年 | 9篇 |
1974年 | 4篇 |
1972年 | 4篇 |
1969年 | 4篇 |
1968年 | 4篇 |
排序方式: 共有4445条查询结果,搜索用时 15 毫秒
101.
102.
Monica Rolando Serena Sanulli Christophe Rusniok Laura Gomez-Valero Clement Bertholet Tobias Sahr Raphael Margueron Carmen Buchrieser 《Cell host & microbe》2013,13(4):395-405
Highlights? Upon infection, L. pneumophila secretes RomA, a SET domain-containing methyltransferase ? RomA triggers H3K14 trimethylation, causing a switch from gene activation to repression ? ChIP-seq identified 4,870 H3K14 methylated promoter regions, including innate immune genes ? RomA SET domain is required for efficient intracellular replication of L. pneumophila 相似文献
103.
Epigenetic dysregulation in the developing Down syndrome cortex 总被引:1,自引:0,他引:1
Nady El Hajj Marcus Dittrich Julia Böck Theo F. J. Kraus Indrajit Nanda Tobias Müller 《Epigenetics》2016,11(8):563-578
104.
Overcoming Electrode‐Induced Losses in Organic Solar Cells by Tailoring a Quasi‐Ohmic Contact to Fullerenes via Solution‐Processed Alkali Hydroxide Layers 下载免费PDF全文
Hong Zhang R. Clayton Shallcross Ning Li Tobias Stubhan Yi Hou Wei Chen Tayebeh Ameri Mathieu Turbiez Neal R. Armstrong Christoph J. Brabec 《Liver Transplantation》2016,6(9)
It is shown that the performance of inverted organic solar cells can be significantly improved by facilitating the formation of a quasi‐ohmic contact via solution‐processed alkali hydroxide (AOH) interlayers on top of n‐type metal oxide (aluminum zinc oxide, AZO, and zinc oxide, ZnO) layers. AOHs significantly reduce the work function of metal oxides, and are further proven to effectively passivate defect states in these metal oxides. The interfacial energetics of these electron collecting contacts with a prototypical electron acceptor (C60) are investigated to reveal the presence of a large interface dipole and a new interface state between the Fermi energy and the C60 highest occupied molecular orbital for AOH‐modified AZO contacts. These novel interfacial gap states are a result of ground‐state electron transfer from the metal hydroxide‐functionalized AZO contact to the adsorbed molecules, which are hypothesized to be electronically hybridized with the contact. These interface states tail all the way to the Fermi energy, providing for a highly n‐doped (metal‐like) interfacial molecular layer. Furthermore, the strong “light‐soaking” effect is no longer observed in devices with a AOH interface. 相似文献
105.
Astrid Grottke Florian Ewald Tobias Lange Dominik N?rz Christiane Herzberger Johanna Bach Nicole Grabinski Lareen Gr?ser Frank H?ppner Bj?rn Nashan Udo Schumacher Manfred Jücker 《PloS one》2016,11(1)
Background
Treatment of breast cancer patients with distant metastases represents one of the biggest challenges in today’s gynecological oncology. Therefore, a better understanding of mechanisms promoting the development of metastases is of paramount importance. The serine/threonine kinase AKT was shown to drive cancer progression and metastasis. However, there is emerging data that single AKT isoforms (i.e. AKT1, AKT2 and AKT3) have different or even opposing functions in the regulation of cancer cell migration in vitro, giving rise to the hypothesis that inhibition of distinct AKT isoforms might have undesirable effects on cancer dissemination in vivo.Methods
The triple negative breast cancer cell line MDA-MB-231 was used to investigate the functional roles of AKT in migration and metastasis. AKT single and double knockdown cells were generated using isoform specific shRNAs. Migration was analyzed using live cell imaging, chemotaxis and transwell assays. The metastatic potential of AKT isoform knockdown cells was evaluated in a subcutaneous xenograft mouse model in vivo.Results
Depletion of AKT3, but not AKT1 or AKT2, resulted in increased migration in vitro. This effect was even more prominent in AKT2,3 double knockdown cells. Furthermore, combined downregulation of AKT2 and AKT3, as well as AKT1 and AKT3 significantly increased metastasis formation in vivo. Screening for promigratory proteins revealed that downregulation of AKT3 increases the expression of S100A4 protein. In accordance, depletion of S100A4 by siRNA approach reverses the increased migration induced by knockdown of AKT3.Conclusions
We demonstrated that knockdown of AKT3 can increase the metastatic potential of triple negative breast cancer cells. Therefore, our results provide a rationale for the development of AKT isoform specific inhibitors. 相似文献106.
Both the concept and the application of the impact factor (IF) have been subject to widespread critique, including concerns over its potential manipulation. This study provides a systematic analysis of significant journal Impact Factor changes, based on the relative contribution of either one or both variables of the IF equation (i.e. citations / articles as the numerator / denominator of the quotient). A cohort of JCR-listed journals which faced the most dramatic absolute IF changes between 2013 and 2014 (ΔIF ≥ 3.0, n = 49) was analyzed for the causes resulting in IF changes that theses journals have experienced in the last five years. Along with the variation by number of articles and citations, this analysis includes the relative change of both variables compared to each other and offers a classification of `valid`and `invalid`scenarios of IF variation in terms of the intended goal of the IF to measure journal quality. The sample cohort features a considerable incidence of IF increases (18%) which are qualified as `invalid`according to this classification because the IF increase is merely based on a favorably changing number of articles (denominator). The results of this analysis point out the potentially delusive effect of IF increases gained through effective shrinkage of publication output. Therefore, careful consideration of the details of the IF equation and possible implementation of control mechanisms versus the volatile factor of number of articles may help to improve the expressiveness of this metric. 相似文献
107.
Sheila N. Balinda Pascale Ondoa Ekwaro A. Obuku Aletta Kliphuis Isaac Egau Michelle Bronze Lordwin Kasambula Rob Schuurman Nicole Spieker Tobias F. Rinke de Wit Cissy Kityo ART–A consortium 《PloS one》2016,11(1)
Background
WHO recommends regular viral load (VL) monitoring of patients on antiretroviral therapy (ART) for timely detection of virological failure, prevention of acquired HIV drug resistance (HIVDR) and avoiding unnecessary switching to second-line ART. However, the cost and complexity of routine VL testing remains prohibitive in most resource limited settings (RLS). We evaluated a simple, low–cost, qualitative viral–failure assay (VFA) on dried blood spots (DBS) in three clinical settings in Uganda.Methods
We conducted a cross–sectional diagnostic accuracy study in three HIV/AIDS treatment centres at the Joint Clinical Research Centre in Uganda. The VFA employs semi-quantitative detection of HIV–1 RNA amplified from the LTR gene. We used paired dry blood spot (DBS) and plasma with the COBASAmpliPrep/COBASTaqMan, Roche version 2 (VLref) as the reference assay. We used the VFA at two thresholds of viral load, (>5,000 or >1,000 copies/ml).Results
496 paired VFA and VLref results were available for comparative analysis. Overall, VFA demonstrated 78.4% sensitivity, (95% CI: 69.7%–87.1%), 93% specificity (95% CI: 89.7%–96.4%), 89.3% accuracy (95% CI: 85%–92%) and an agreement kappa = 0.72 as compared to the VLref. The predictive values of positivity and negativity among patients on ART for >12 months were 72.7% and 99.3%, respectively.Conclusions
VFA allowed 89% of correct classification of VF. Only 11% of the patients were misclassified with the potential of unnecessary or late switch to second–line ART. Our findings present an opportunity to roll out simple and affordable VL monitoring for HIV–1 treatment in RLS. 相似文献108.
Ann Lindstrand Joan Kalyango Tobias Alfvén Jessica Darenberg Daniel Kadobera Freddie Bwanga Stefan Peterson Birgitta Henriques-Normark Karin K?llander 《PloS one》2016,11(11)
BackgroundPneumonia is the major cause of death in children globally, with more than 900,000 deaths annually in children under five years of age. Streptococcus pneumoniae causes most deaths, most often in the form of community acquired pneumonia. Pneumococcal conjugate vaccines (PCVs) are currently being implemented in many low-income countries. PCVs decrease vaccine-type pneumococcal carriage, a prerequisite for invasive pneumococcal disease, and thereby affects pneumococcal disease and transmission. In Uganda, PCV was launched in 2014, but baseline data is lacking for pneumococcal serotypes in carriage.ObjectivesTo study pneumococcal nasopharyngeal carriage and serotype distribution in children under 5 years of age prior to PCV introduction in UgandaMethodsThree cross-sectional pneumococcal carriage surveys were conducted in 2008, 2009 and 2011, comprising respectively 150, 587 and 1024 randomly selected children aged less than five years from the Iganga/Mayuge Health and Demographic Surveillance Site. The caretakers were interviewed about illness history of the child and 1723 nasopharyngeal specimens were collected. From these, 927 isolates of S. pneumoniae were serotyped.ResultsOverall, the carriage rate of S. pneumoniae was 56% (957/1723). Pneumococcal carriage was associated with illness on the day of the interview (OR = 1.50, p = 0.04). The most common pneumococcal serotypes were in descending order 19F (16%), 23F (9%), 6A (8%), 29 (7%) and 6B (7%). One percent of the strains were non-typeable. The potential serotype coverage rate for PCV10 was 42% and 54% for PCV13.ConclusionAbout half of circulating pneumococcal serotypes in carriage in the Ugandan under-five population studied was covered by available PCVs. 相似文献
109.
Patrick Horn Gülsüm Erkilet Verena Veulemans Patric Kr?pil Leon Schurgers Tobias Zeus Christian Heiss Malte Kelm Ralf Westenfeld 《PloS one》2016,11(3)
Background
Circulating microparticles (MPs) derived from endothelial cells and blood cells bear procoagulant activity and promote thrombin generation. Thrombin exerts proinflammatory effects mediating the progression of atherosclerosis. Aortic valve stenosis may represent an atherosclerosis-like process involving both the aortic valve and the vascular system. The aim of this study was to investigate whether MP-induced thrombin generation is related to coronary atherosclerosis and aortic valve calcification.Methods
In a cross-sectional study of 55 patients with severe aortic valve stenosis, we assessed the coronary calcification score (CAC) as indicator of total coronary atherosclerosis burden, and aortic valve calcification (AVC) by computed tomography. Thrombin-antithrombin complex (TATc) levels were measured as a marker for thrombin formation. Circulating MPs were characterized by flow cytometry according to the expression of established surface antigens and by measuring MP-induced thrombin generation.Results
Patients with CAC score below the median were classified as patients with low CAC, patients with CAC Score above the median as high CAC. In patients with high CAC compared to patients with low CAC we detected higher levels of TATc, platelet-derived MPs (PMPs), endothelial-derived MPs (EMPs) and MP-induced thrombin generation. Increased level of PMPs and MP-induced thrombin generation were independent predictors for the severity of CAC. In contrast, AVC Score did not differ between patients with high and low CAC and did neither correlate with MPs levels nor with MP-induced thrombin generation.Conclusion
In patients with severe aortic valve stenosis MP-induced thrombin generation was independently associated with the severity of CAC but not AVC indicating different pathomechanisms involved in coronary artery and aortic valve calcification. 相似文献110.
Guillaume Bonnier Tobias Kober Myriam Schluep Renaud Du Pasquier Gunnar Krueger Reto Meuli Cristina Granziera Alexis Roche 《PloS one》2016,11(2)