全文获取类型
收费全文 | 1839篇 |
免费 | 132篇 |
国内免费 | 3篇 |
出版年
2023年 | 4篇 |
2022年 | 23篇 |
2021年 | 35篇 |
2020年 | 31篇 |
2019年 | 29篇 |
2018年 | 34篇 |
2017年 | 28篇 |
2016年 | 47篇 |
2015年 | 92篇 |
2014年 | 107篇 |
2013年 | 136篇 |
2012年 | 146篇 |
2011年 | 169篇 |
2010年 | 77篇 |
2009年 | 64篇 |
2008年 | 91篇 |
2007年 | 80篇 |
2006年 | 85篇 |
2005年 | 83篇 |
2004年 | 57篇 |
2003年 | 59篇 |
2002年 | 49篇 |
2001年 | 41篇 |
2000年 | 35篇 |
1999年 | 35篇 |
1998年 | 8篇 |
1997年 | 18篇 |
1996年 | 11篇 |
1995年 | 22篇 |
1994年 | 7篇 |
1993年 | 14篇 |
1992年 | 27篇 |
1991年 | 25篇 |
1990年 | 30篇 |
1989年 | 10篇 |
1988年 | 25篇 |
1987年 | 17篇 |
1986年 | 10篇 |
1985年 | 17篇 |
1984年 | 8篇 |
1983年 | 6篇 |
1982年 | 9篇 |
1981年 | 7篇 |
1980年 | 4篇 |
1979年 | 11篇 |
1978年 | 6篇 |
1975年 | 5篇 |
1974年 | 7篇 |
1973年 | 7篇 |
1972年 | 5篇 |
排序方式: 共有1974条查询结果,搜索用时 15 毫秒
931.
Lee VJ Yap J Cook AR Tan CH Loh JP Koh WH Lim EA Liaw JC Chew JS Hossain I Chan KW Ting PJ Ng SH Gao Q Kelly PM Chen MI Tambyah PA Tan BH 《PloS one》2011,6(3):e17468
Introduction
Influenza infections present with wide-ranging clinical features. We aim to compare the differences in presentation between influenza and non-influenza cases among those with febrile respiratory illness (FRI) to determine predictors of influenza infection.Methods
Personnel with FRI (defined as fever≥37.5°C, with cough or sore throat) were recruited from the sentinel surveillance system in the Singapore military. Nasal washes were collected, and tested using the Resplex II and additional PCR assays for etiological determination. Interviewer-administered questionnaires collected information on patient demographics and clinical features. Univariate comparison of the various parameters was conducted, with statistically significant parameters entered into a multivariate logistic regression model. The final multivariate model for influenza versus non-influenza cases was used to build a predictive probability clinical diagnostic model.Results
821 out of 2858 subjects recruited from 11 May 2009 to 25 Jun 2010 had influenza, of which 434 (52.9%) had 2009 influenza A (H1N1), 58 (7.1%) seasonal influenza A (H3N2) and 269 (32.8%) influenza B. Influenza-positive cases were significantly more likely to present with running nose, chills and rigors, ocular symptoms and higher temperature, and less likely with sore throat, photophobia, injected pharynx, and nausea/vomiting. Our clinical diagnostic model had a sensitivity of 65% (95% CI: 58%, 72%), specificity of 69% (95% CI: 62%, 75%), and overall accuracy of 68% (95% CI: 64%, 71%), performing significantly better than conventional influenza-like illness (ILI) criteria.Conclusions
Use of a clinical diagnostic model may help predict influenza better than the conventional ILI definition among young adults with FRI. 相似文献932.
Poly-(D,L-lactide-co-glycolide) (PLGA) nanoparticles have been widely studied for drug delivery. The aim of this study is to determine how cellular uptake of these nanoparticles is influenced by different surface properties, incubation time, particle concentration and cell types. Spherical coumarin-6 loaded PLGA nanoparticles with a size of about 100 nm were synthesized through solvent emulsion evaporation and nanoprecipitation methods. In vitro cellular uptake efficiency was determined using human bronchial epithelial cells (BEAS-2B) and murine monocyte-derived macrophage (RAW264.7) cells. PLGA nanoparticles were incubated with these cells in a concentration range of 10-300 μg/ml for different time periods. The results show that cellular uptake decreased for nanoparticles surface coated with PVA surfactant and was especially limited for severely aggregated particles. At higher particle concentration, the total amount of particles taken up by cells increased while the uptake efficiency decreased. In addition, cells could take up more particles with longer incubation time, although the uptake rate decreased gradually with time. Finally, RAW264.7 cells show increased uptake compared to BEAS-2B cells. The information drawn from this study would provide important clues on how nanomaterials interact with cells and how these interactions can influence biocompatibility or toxicity. 相似文献
933.
McCutcheon S Alejo Blanco AR Houston EF de Wolf C Tan BC Smith A Groschup MH Hunter N Hornsey VS MacGregor IR Prowse CV Turner M Manson JC 《PloS one》2011,6(8):e23169
Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion. 相似文献
934.
Cytoadherence or sequestration is essential for the pathogenesis of the most virulent human malaria species, Plasmodium falciparum (P. falciparum). Similar to leukocyte-endothelium interaction in response to inflammation, cytoadherence of P. falciparum infected red blood cells (IRBCs) to endothelium occurs under physiological shear stresses in blood vessels and involves an array of molecule complexes which cooperate to form stable binding. Here, we applied single-molecule force spectroscopy technique to quantify the dynamic force spectra and characterize the intrinsic kinetic parameters for specific ligand-receptor interactions involving two endothelial receptor proteins: thrombospondin (TSP) and CD36. It was shown that CD36 mediated interaction was much more stable than that mediated by TSP at single molecule level, although TSP-IRBC interaction appeared stronger than CD36-IRBC interaction in the high pulling rate regime. This suggests that TSP-mediated interaction may initiate cell adhesion by capturing the fast flowing IRBCs whereas CD36 functions as the 'holder' for providing stable binding. 相似文献
935.
936.
We show, contrary to expectation, that the trajectory predicted by general-relativistic mechanics for a low-speed weak-gravity system is not always well-approximated by the trajectories predicted by special-relativistic and newtonian mechanics for the same parameters and initial conditions. If the system is dissipative, the breakdown of agreement occurs for chaotic trajectories only. If the system is non-dissipative, the breakdown of agreement occurs for chaotic trajectories and non-chaotic trajectories. The agreement breaks down slowly for non-chaotic trajectories but rapidly for chaotic trajectories. When the predictions are different, general-relativistic mechanics must therefore be used, instead of special-relativistic mechanics (newtonian mechanics), to correctly study the dynamics of a weak-gravity system (a low-speed weak-gravity system). 相似文献
937.
van der Vlugt LE Labuda LA Ozir-Fazalalikhan A Lievers E Gloudemans AK Liu KY Barr TA Sparwasser T Boon L Ngoa UA Feugap EN Adegnika AA Kremsner PG Gray D Yazdanbakhsh M Smits HH 《PloS one》2012,7(2):e30883
Chronic helminth infections, such as schistosomes, are negatively associated with allergic disorders. Here, using B cell IL-10-deficient mice, Schistosoma mansoni-mediated protection against experimental ovalbumin-induced allergic airway inflammation (AAI) was shown to be specifically dependent on IL-10-producing B cells. To study the organs involved, we transferred B cells from lungs, mesenteric lymph nodes or spleen of OVA-infected mice to recipient OVA-sensitized mice, and showed that both lung and splenic B cells reduced AAI, but only splenic B cells in an IL-10-dependent manner. Although splenic B cell protection was accompanied by elevated levels of pulmonary FoxP3(+) regulatory T cells, in vivo ablation of FoxP3(+) T cells only moderately restored AAI, indicating an important role for the direct suppressory effect of regulatory B cells. Splenic marginal zone CD1d(+) B cells proved to be the responsible splenic B cell subset as they produced high levels of IL-10 and induced FoxP3(+) T cells in vitro. Indeed, transfer of CD1d(+) MZ-depleted splenic B cells from infected mice restored AAI. Markedly, we found a similarly elevated population of CD1d(hi) B cells in peripheral blood of Schistosoma haematobium-infected Gabonese children compared to uninfected children and these cells produced elevated levels of IL-10. Importantly, the number of IL-10-producing CD1d(hi) B cells was reduced after anti-schistosome treatment. This study points out that in both mice and men schistosomes have the capacity to drive the development of IL-10-producing regulatory CD1d(hi) B cells and furthermore, these are instrumental in reducing experimental allergic inflammation in mice. 相似文献
938.
Epithelial Mesenchymal Transition (EMT) is a crucial mechanism for carcinoma progression, as it provides routes for in situ carcinoma cells to dissociate and become motile, leading to localized invasion and metastatic spread. Targeting EMT therefore represents an important therapeutic strategy for cancer treatment. The discovery of oncogene addiction in sustaining tumor growth has led to the rapid development of targeted therapeutics. Whilst initially optimized as anti-proliferative agents, it is likely that some of these compounds may inhibit EMT initiation or sustenance, since EMT is also modulated by similar signaling pathways that these compounds were designed to target. We have developed a novel screening assay that can lead to the identification of compounds that can inhibit EMT initiated by growth factor signaling. This assay is designed as a high-content screening assay where both cell growth and cell migration can be analyzed simultaneously via time-course imaging in multi-well plates. Using this assay, we have validated several compounds as viable EMT inhibitors. In particular, we have identified compounds targeting ALK5, MEK, and SRC as potent inhibitors that can interfere with EGF, HGF, and IGF-1 induced EMT signaling. Overall, this EMT screening method provides a foundation for improving the therapeutic value of recently developed compounds in advanced stage carcinoma. 相似文献
939.
DJ Corsi SV Subramanian M McKee W Li S Swaminathan P Lopez-Jaramillo A Avezum SA Lear G Dagenais S Rangarajan K Teo S Yusuf CK Chow 《PloS one》2012,7(9):e44410
BACKGROUND: Public health research has turned towards examining upstream, community-level determinants of cardiovascular disease risk factors. Objective measures of the environment, such as those derived from direct observation, and perception-based measures by residents have both been associated with health behaviours. However, current methods are generally limited to objective measures, often derived from administrative data, and few instruments have been evaluated for use in rural areas or in low-income countries. We evaluate the reliability of a quantitative tool designed to capture perceptions of community tobacco, nutrition, and social environments obtained from interviews with residents in communities in 5 countries. METHODOLOGY/ PRINCIPAL FINDINGS: Thirteen measures of the community environment were developed from responses to questionnaire items from 2,360 individuals residing in 84 urban and rural communities in 5 countries (China, India, Brazil, Colombia, and Canada) in the Environmental Profile of a Community's Health (EPOCH) study. Reliability and other properties of the community-level measures were assessed using multilevel models. High reliability (>0.80) was demonstrated for all community-level measures at the mean number of survey respondents per community (n?=?28 respondents). Questionnaire items included in each scale were found to represent a common latent factor at the community level in multilevel factor analysis models. CONCLUSIONS/ SIGNIFICANCE: Reliable measures which represent aspects of communities potentially related to cardiovascular disease (CVD)/risk factors can be obtained using feasible sample sizes. The EPOCH instrument is suitable for use in different settings to explore upstream determinants of CVD/risk factors. 相似文献
940.