全文获取类型
收费全文 | 3534篇 |
免费 | 315篇 |
国内免费 | 2篇 |
专业分类
3851篇 |
出版年
2023年 | 12篇 |
2022年 | 44篇 |
2021年 | 67篇 |
2020年 | 34篇 |
2019年 | 49篇 |
2018年 | 78篇 |
2017年 | 56篇 |
2016年 | 121篇 |
2015年 | 180篇 |
2014年 | 185篇 |
2013年 | 212篇 |
2012年 | 301篇 |
2011年 | 276篇 |
2010年 | 173篇 |
2009年 | 162篇 |
2008年 | 196篇 |
2007年 | 217篇 |
2006年 | 174篇 |
2005年 | 172篇 |
2004年 | 141篇 |
2003年 | 134篇 |
2002年 | 135篇 |
2001年 | 31篇 |
2000年 | 25篇 |
1999年 | 37篇 |
1998年 | 33篇 |
1997年 | 33篇 |
1996年 | 19篇 |
1995年 | 19篇 |
1994年 | 22篇 |
1993年 | 20篇 |
1992年 | 30篇 |
1991年 | 36篇 |
1990年 | 22篇 |
1988年 | 16篇 |
1987年 | 17篇 |
1986年 | 13篇 |
1985年 | 27篇 |
1984年 | 22篇 |
1983年 | 19篇 |
1982年 | 12篇 |
1980年 | 12篇 |
1979年 | 13篇 |
1978年 | 12篇 |
1975年 | 14篇 |
1974年 | 15篇 |
1973年 | 14篇 |
1972年 | 16篇 |
1969年 | 18篇 |
1967年 | 12篇 |
排序方式: 共有3851条查询结果,搜索用时 0 毫秒
71.
Jorge Lizandra José Devís-Devís Esther Pérez-Gimeno Alexandra Valencia-Peris Carmen Peiró-Velert 《PloS one》2016,11(4)
This study examined whether adolescents’ time spent on sedentary behaviors (academic, technological-based and social-based activities) was a better predictor of academic performance than the reverse. A cohort of 755 adolescents participated in a three-year period study. Structural Equation Modeling techniques were used to test plausible causal hypotheses. Four competing models were analyzed to determine which model best fitted the data. The Best Model was separately tested by gender. The Best Model showed that academic performance was a better predictor of sedentary behaviors than the other way round. It also indicated that students who obtained excellent academic results were more likely to succeed academically three years later. Moreover, adolescents who spent more time in the three different types of sedentary behaviors were more likely to engage longer in those sedentary behaviors after the three-year period. The better the adolescents performed academically, the less time they devoted to social-based activities and more to academic activities. An inverse relationship emerged between time dedicated to technological-based activities and academic sedentary activities. A moderating auto-regressive effect by gender indicated that boys were more likely to spend more time on technological-based activities three years later than girls. To conclude, previous academic performance predicts better sedentary behaviors three years later than the reverse. The positive longitudinal auto-regressive effects on the four variables under study reinforce the ‘success breeds success’ hypothesis, with academic performance and social-based activities emerging as the strongest ones. Technological-based activities showed a moderating effect by gender and a negative longitudinal association with academic activities that supports a displacement hypothesis. Other longitudinal and covariate effects reflect the complex relationships among sedentary behaviors and academic performance and the need to explore these relationships in depth. Theoretical and practical implications for school health are outlined. 相似文献
72.
Cyclolipopeptides derived from the antimicrobial peptide c(Lys-Lys-Leu-Lys-Lys-Phe-Lys-Lys-Leu-Gln) (BPC194) were prepared on solid-phase and screened against four plant pathogens. The incorporation at Lys5 of fatty acids of 4 to 9 carbon atoms led to active cyclolipopeptides. The influence on the antimicrobial activity of the Lys residue that is derivatized was also evaluated. In general, acylation of Lys1, Lys2 or Lys5 rendered the sequences with the highest activity. Incorporation of a D-amino acid maintained the antimicrobial activity while significantly reduced the hemolysis. Replacement of Phe with a His also yielded cyclolipopeptides with low hemolytic activity. Derivatives exhibiting low phytotoxicity in tobacco leaves were also found. Interestingly, sequences with or without significant activity against phytopathogenic bacteria and fungi, but with differential hemolysis and phytotoxicity were identified. Therefore, this study represents an approach to the development of bioactive peptides with selective activity against microbial, plant and animal cell targets. These selective cyclolipopeptides are candidates useful not only to combat plant pathogens but also to be applied in other fields. 相似文献
73.
Emily E. I. M. Mouser Georgios Pollakis Maria Yazdanbakhsh William Harnett Esther C. de Jong William A. Paxton 《PloS one》2016,11(1)
One of the hallmarks of HIV-1 disease is the association of heightened CD4+ T-cell activation with HIV-1 replication. Parasitic helminths including filarial nematodes have evolved numerous and complex mechanisms to skew, dampen and evade human immune responses suggesting that HIV-1 infection may be modulated in co-infected individuals. Here we studied the effects of two filarial nematode products, adult worm antigen from Brugia malayi (BmA) and excretory-secretory product 62 (ES-62) from Acanthocheilonema viteae on HIV-1 infection in vitro. Neither BmA nor ES-62 influenced HIV-1 replication in CD4+ enriched T-cells, with either a CCR5- or CXCR4-using virus. BmA, but not ES-62, had the capacity to bind the C-type lectin dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) thereby inhibiting HIV-1 trans-infection of CD4+ enriched T-cells. As for their effect on DCs, neither BmA nor ES-62 could enhance or inhibit DC maturation as determined by CD83, CD86 and HLA-DR expression, or the production of IL-6, IL-10, IL-12 and TNF-α. As expected, due to the unaltered DC phenotype, no differences were found in CD4+ T helper (Th) cell phenotypes induced by DCs treated with either BmA or ES-62. Moreover, the HIV-1 susceptibility of the Th-cell populations induced by BmA or ES-62 exposed DCs was unaffected for both CCR5- and CXCR4-using HIV-1 viruses. In conclusion, although BmA has the potential capacity to interfere with HIV-1 transmission or initial viral dissemination through preventing the virus from interacting with DCs, no differences in the Th-cell polarizing capacity of DCs exposed to BmA or ES-62 were observed. Neither antigenic source demonstrated beneficial or detrimental effects on the HIV-1 susceptibility of CD4+ Th-cells induced by exposed DCs. 相似文献
74.
Verónica García-Alonso Esther Titos Jose Alcaraz-Quiles Bibiana Rius Aritz Lopategi Cristina López-Vicario Per-Johan Jakobsson Salvadora Delgado Juanjo Lozano Joan Clària 《PloS one》2016,11(4)
Obesity induces white adipose tissue (WAT) dysfunction characterized by unremitting inflammation and fibrosis, impaired adaptive thermogenesis and increased lipolysis. Prostaglandins (PGs) are powerful lipid mediators that influence the homeostasis of several organs and tissues. The aim of the current study was to explore the regulatory actions of PGs in human omental WAT collected from obese patients undergoing laparoscopic bariatric surgery. In addition to adipocyte hypertrophy, obese WAT showed remarkable inflammation and total and pericellular fibrosis. In this tissue, a unique molecular signature characterized by altered expression of genes involved in inflammation, fibrosis and WAT browning was identified by microarray analysis. Targeted LC-MS/MS lipidomic analysis identified increased PGE2 levels in obese fat in the context of a remarkable COX-2 induction and in the absence of changes in the expression of terminal prostaglandin E synthases (i.e. mPGES-1, mPGES-2 and cPGES). IPA analysis established PGE2 as a common top regulator of the fibrogenic/inflammatory process present in this tissue. Exogenous addition of PGE2 significantly reduced the expression of fibrogenic genes in human WAT explants and significantly down-regulated Col1α1, Col1α2 and αSMA in differentiated 3T3 adipocytes exposed to TGF-β. In addition, PGE2 inhibited the expression of inflammatory genes (i.e. IL-6 and MCP-1) in WAT explants as well as in adipocytes challenged with LPS. PGE2 anti-inflammatory actions were confirmed by microarray analysis of human pre-adipocytes incubated with this prostanoid. Moreover, PGE2 induced expression of brown markers (UCP1 and PRDM16) in WAT and adipocytes, but not in pre-adipocytes, suggesting that PGE2 might induce the trans-differentiation of adipocytes towards beige/brite cells. Finally, PGE2 inhibited isoproterenol-induced adipocyte lipolysis. Taken together, these findings identify PGE2 as a regulator of the complex network of interactions driving uncontrolled inflammation and fibrosis and impaired adaptive thermogenesis and lipolysis in human obese visceral WAT. 相似文献
75.
Esther H. D. Carlitz Robert Miller Clemens Kirschbaum Wei Gao Daniel C. H?nni Carel P. van Schaik 《PloS one》2016,11(4)
Non-human primates face major environmental changes due to increased human impacts all over the world. Although some species are able to survive in certain landscapes with anthropogenic impact, their long-term viability and fitness may be decreased due to chronic stress. Here we assessed long-term stress levels through cortisol analysis in chimpanzee hair obtained from sleeping nests in northwestern Uganda, in order to estimate welfare in the context of ecotourism, forest fragmentation with human-wildlife conflicts, and illegal logging with hunting activity (albeit not of primates), compared with a control without human contact or conflict. Concerning methodological issues, season [F(2,129) = 37.4, p < 0.0001, r2 = 0.18] and the age of nests [F(2,178) = 20.3, p < 0.0001, r2 = 0.11] significantly predicted hair cortisol concentrations (HCC). With regard to effects of anthropogenic impacts, our results neither showed elevation of HCC due to ecotourism, nor due to illegal logging compared to their control groups. We did, however, find significantly increased HCC in the fragment group compared to chimpanzees living in a nearby intact forest [F(1,88) = 5.0, p = 0.03, r2 = 0.20]. In conclusion, our results suggest that hair cortisol analysis is a powerful tool that can help understanding the impact of anthropogenic disturbances on chimpanzee well-being and could be applied to other great ape species. 相似文献
76.
Gemma Chiva-Blanch Rosa Suades Javier Crespo Esther Pe?a Teresa Padró Elena Jiménez-Xarrié Joan Martí-Fàbregas Lina Badimon 《PloS one》2016,11(1)
Purpose
Ischemic stroke has shown to induce platelet and endothelial microparticle shedding, but whether stroke induces microparticle shedding from additional blood and vascular compartment cells is unclear. Neural precursor cells have been shown to replace dying neurons at sites of brain injury; however, if neural precursor cell activation is associated to microparticle shedding, and whether this activation is maintained at long term and associates to stroke type and severity remains unknown. We analyzed neural precursor cells and blood and vascular compartment cells microparticle shedding after an acute ischemic stroke.Methods
Forty-four patients were included in the study within the first 48h after the onset of stroke. The cerebral lesion size was evaluated at 3–7 days of the stroke. Circulating microparticles from neural precursor cells and blood and vascular compartment cells (platelets, endothelial cells, erythrocytes, leukocytes, lymphocytes, monocytes and smooth muscle cells) were analyzed by flow cytometry at the onset of stroke and at 7 and 90 days. Forty-four age-matched high cardiovascular risk subjects without documented vascular disease were used as controls.Results
Compared to high cardiovascular risk controls, patients showed higher number of neural precursor cell- and all blood and vascular compartment cell-derived microparticles at the onset of stroke, and after 7 and 90 days. At 90 days, neural precursor cell-derived microparticles decreased and smooth muscle cell-derived microparticles increased compared to levels at the onset of stroke, but only in those patients with the highest stroke-induced cerebral lesions.Conclusions
Stroke increases blood and vascular compartment cell and neural precursor cell microparticle shedding, an effect that is chronically maintained up to 90 days after the ischemic event. These results show that stroke induces a generalized blood and vascular cell activation and the initiation of neuronal cell repair process after stroke. Larger cerebral lesions associate with deeper vessel injury affecting vascular smooth muscle cells. 相似文献77.
Silvia Castellanos-Castro Carlos M. Cerda-García-Rojas Rosario Javier-Reyna Jonnatan Pais-Morales Bibiana Chávez-Munguía Esther Orozco 《Biochemistry and Biophysics Reports》2016
Phospholipids are essential for vesicle fusion and fission and both are fundamental events for Entamoeba histolytica phagocytosis. Our aim was to identify the lysobisphosphatidic acid (LBPA) in trophozoites and investigate its cellular fate during endocytosis. LBPA was detected by TLC in a 0.5 Rf spot of total lipids, which co-migrated with the LBPA standard. The 6C4 antibody, against LBPA recognized phospholipids extracted from this spot. Reverse phase LC-ESI-MS and MS/MS mass spectrometry revealed six LBPA species of m/z 772.58–802.68. LBPA was associated to pinosomes and phagosomes. Intriguingly, during pinocytosis, whole cell fluorescence quantification showed that LBPA dropped 84% after 15 min incubation with FITC-Dextran, and after 60 min, it increased at levels close to steady state conditions. Similarly, during erythrophagocytosis, after 15 min, LBPA also dropped in 36% and increased after 60 and 90 min. EhRab7A protein appeared in some vesicles with LBPA in steady state conditions, but after phagocytosis co-localization of both molecules increased and in late phases of erythrophagocytosis they were found in huge phagosomes or multivesicular bodies with many intraluminal vacuoles, and surrounding ingested erythrocytes and phagosomes. The 6C4 and anti-EhADH (EhADH is an ALIX family protein) antibodies and Lysotracker merged in about 50% of the vesicles in steady state conditions and throughout phagocytosis. LBPA and EhADH were also inside huge phagosomes. These results demonstrated that E. histolytica LBPA is associated to pinosomes and phagosomes during endocytosis and suggested differences of LBPA requirements during pinocytosis and phagocytosis. 相似文献
78.
79.
80.