全文获取类型
收费全文 | 537篇 |
免费 | 34篇 |
国内免费 | 2篇 |
出版年
2023年 | 1篇 |
2022年 | 1篇 |
2021年 | 14篇 |
2020年 | 1篇 |
2019年 | 3篇 |
2018年 | 9篇 |
2017年 | 8篇 |
2016年 | 11篇 |
2015年 | 19篇 |
2014年 | 15篇 |
2013年 | 33篇 |
2012年 | 52篇 |
2011年 | 43篇 |
2010年 | 27篇 |
2009年 | 23篇 |
2008年 | 43篇 |
2007年 | 38篇 |
2006年 | 39篇 |
2005年 | 32篇 |
2004年 | 25篇 |
2003年 | 29篇 |
2002年 | 28篇 |
2001年 | 11篇 |
2000年 | 6篇 |
1999年 | 3篇 |
1998年 | 8篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 4篇 |
1991年 | 5篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 4篇 |
1986年 | 4篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 4篇 |
1981年 | 2篇 |
1979年 | 1篇 |
1978年 | 3篇 |
1977年 | 1篇 |
1975年 | 2篇 |
1973年 | 1篇 |
1969年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有573条查询结果,搜索用时 15 毫秒
81.
Group A streptococcus is a Gram-positive bacteria that causes a range of infectious diseases. Targeting the bacteria, a new self-adjuvanting vaccine candidate, incorporating a carbohydrate carrier and an amino acid-based adjuvant, was synthesised utilising carbohydrate chemistry and solid-phase peptide synthesis procedures. Characterisation of the candidate was achieved using reverse-phase HPLC and electrospray ionisation mass spectrometry. The successful synthesis and characterisation of the vaccine candidate may contribute to the discovery of a therapeutically and clinically viable vaccine against group A streptococcus. 相似文献
82.
Kitti Pazmandi Brahma V. Kumar Krisztina Szabo Istvan Boldogh Arpad Szoor Gyorgy Vereb Agota Veres Arpad Lanyi Eva Rajnavolgyi Attila Bacsi 《PloS one》2012,7(12)
Ragweed (Ambrosia artemisiifolia) pollen grains, which are generally considered too large to reach the lower respiratory tract, release subpollen particles (SPPs) of respirable size upon hydration. These SPPs contain allergenic proteins and functional NAD(P)H oxidases. In this study, we examined whether exposure to SPPs initiates the activation of human monocyte-derived dendritic cells (moDCs). We found that treatment with freshly isolated ragweed SPPs increased the intracellular levels of reactive oxygen species (ROS) in moDCs. Phagocytosis of SPPs by moDCs, as demonstrated by confocal laser-scanning microscopy, led to an up-regulation of the cell surface expression of CD40, CD80, CD86, and HLA-DQ and an increase in the production of IL-6, TNF-α, IL-8, and IL-10. Furthermore, SPP-treated moDCs had an increased capacity to stimulate the proliferation of naïve T cells. Co-culture of SPP-treated moDCs with allogeneic CD3+ pan-T cells resulted in increased secretion of IFN-γ and IL-17 by T cells of both allergic and non-allergic subjects, but induced the production of IL-4 exclusively from the T cells of allergic individuals. Addition of exogenous NADPH further increased, while heat-inactivation or pre-treatment with diphenyleneiodonium (DPI), an inhibitor of NADPH oxidases, strongly diminished, the ability of SPPs to induce phenotypic and functional changes in moDCs, indicating that these processes were mediated, at least partly, by the intrinsic NAD(P)H oxidase activity of SPPs. Collectively, our data suggest that inhaled ragweed SPPs are fully capable of activating dendritic cells (DCs) in the airways and SPPs'' NAD(P)H oxidase activity is involved in initiation of adaptive immune responses against innocuous pollen proteins. 相似文献
83.
84.
Sherborne Neil Miller Joel C. Blyuss Konstantin B. Kiss Istvan Z. 《Journal of mathematical biology》2018,76(3):755-778
Journal of Mathematical Biology - This paper introduces a novel extension of the edge-based compartmental model to epidemics where the transmission and recovery processes are driven by general... 相似文献
85.
86.
Heterogeneity in host susceptibility and transmissibility to parasite attack allows a lower transmission rate to sustain an epidemic than is required in homogeneous host populations. However, this heterogeneity can leave some hosts with little susceptibility to disease, and at high transmission rates, epidemic size can be smaller than for diseases where the host population is homogeneous. In a heterogeneous host population, we model natural selection in a parasite population where host heterogeneity is exploited by different strains to varying degrees. This partitioning of the host population allows coexistence of competing parasite strains, with the heterogeneity-exploiting strains infecting the more susceptible hosts, in the absence of physiological tradeoffs and spatial heterogeneity, and even for markedly different transmission rates. In our model, intermediate-strategy parasites were selected against: should coexistence occur, an equilibrium is reached where strains occupied only the extreme ends of trait space, under appropriate conditions selecting for lower R0 . 相似文献
87.
Pacher Pal Kecskemeti Valeria Ronai Andras Z. Balogh Istvan Gabor Gabor Matkovics Bela 《Molecular and cellular biochemistry》1998,187(1-2):183-190
Human placental syncytiotrophoblast basal membrane plays an important role in transfer of nutrients from the mother to the growing fetus all throughout gestation. The membrane lipid composition together with the bilayer fluidity is found to be the major index in modulation of these transport processes. In the present study, the effects of changing lipid composition on the placental basal membrane fluidity and the modulating influence of the latter on membrane enzyme and transport functions with progress of gestation,were investigated. Steady-state fluorescence analysis using 1,6-diphenyl-1,3,5 hexatriene as the probe, indicated a decrease in fluorescence anisotropy of both labeled native membrane vesicles and liposomes prepared from lipids extracted from the basal membrane vesicles, signifying increased bilayer fluidity with progress of gestation. This in turn, was successfully correlated to the lowering of cholesterol content and enhanced phospholipid concentration with a steady decrease in cholesterol/phospholipid ratio during placental development. Enhanced Na+-K+-ATPase activity and steady-state glucose uptake across basal membrane with gestational progress suggested modulation of membrane protein functions by the fluidity, which was further corroborated by the increased bilayer fluidity and enzyme activity in benzyl alcohol treated basal membrane in each gestational age group. 相似文献
88.
Frequent genes in rare diseases: panel‐based next generation sequencing to disclose causal mutations in hereditary neuropathies 下载免费PDF全文
Maike F. Dohrn Nicola Glöckle Lejla Mulahasanovic Corina Heller Julia Mohr Christine Bauer Erik Riesch Andrea Becker Florian Battke Konstanze Hörtnagel Thorsten Hornemann Saranya Suriyanarayanan Markus Blankenburg Jörg B. Schulz Kristl G. Claeys Burkhard Gess Istvan Katona Andreas Ferbert Debora Vittore Alexander Grimm Stefan Wolking Ludger Schöls Holger Lerche G. Christoph Korenke Dirk Fischer Bertold Schrank Urania Kotzaeridou Gerhard Kurlemann Bianca Dräger Anja Schirmacher Peter Young Beate Schlotter‐Weigel Saskia Biskup 《Journal of neurochemistry》2017,143(5):507-522
89.
Khairul A. Kamaruzaman Peter M. Moyle Istvan Toth 《International journal of peptide research and therapeutics》2017,23(1):119-134
Gene therapy is a promising means to treat or prevent diseases either through gene silencing or expression. Some of the most effective delivery agents are polycationic dendrimers, which are highly branched constructs incorporating many positively charged groups. Two of the most effective dendrimers are polyethyleneimine (PEI) and poly(amidoamine) (PAMAM), which show high proficiency at overcoming barriers to oligonucleotide delivery. However, because of their abundance of cationic charge, they are associated with severe toxicity. We have therefore aimed to develop a low toxicity oligonucleotide delivery system, incorporating multiple components that have been selected and optimised to overcome the barriers to efficient oligonucleotide delivery. In this work we have focused on improving the toxicity, cellular uptake, and condensation of plasmid DNA (pDNA) through the fusion of synthetic poly-l-lysine (PLL) dendrons with the cell penetrating peptide TAT(48-60). A library of dendron structures, from 4+ to 16+ charge, and constructs containing six histidine residues, were synthesised. The effects of each modification on pDNA binding and condensation; cellular uptake and toxicity; and the size and zeta-potential of the complexes were assessed to identify the optimum dendron for incorporation into our systems. This work concluded that increasing the dendron charge from 4+ to 16+ significantly improved cellular uptake and pDNA condensation, with no effect on toxicity, while PLL dendrons with greater than 16+ charge could not be efficiently produced. In comparison, the incorporation of six histidines into these constructs had a variable effect on cellular uptake, and generated larger sized complexes, but did not affect toxicity. 相似文献
90.
Biochemical assay-based selectivity profiling of clinically relevant kinase inhibitors on mutant forms of EGF receptor 总被引:1,自引:0,他引:1
Varkondi E Pinter F Robert K Schwab R Breza N Orfi L Keri G Petak I 《Journal of receptor and signal transduction research》2008,28(3):295-306
Gefitinib and erlotinib are potent EGFR tyrosine kinase inhibitors (potentially) useful for the treatment of non-small-cell lung cancer (NSCLC). Clinical responses, however, in NSCLC patients have been linked to the presence of certain activating mutations of EGFR. We used an ELISA-based biochemical assay to confirm the selective inhibitory efficacy of gefitinib and erlotinib on the activated mutant receptor. Our results are in line with the clinical observations providing evidence for the predictive power of the kinase assay. Four additional compounds were also investigated: CI-1033 and EKB-569 had dramatic inhibitory effects on all EGFR forms, whereas PD153035 and AG1478 were active on wild-type and activating mutant protein. In docking simulations with wild-type EGFR, our inhibitory data are in good agreement with the binding scores. These data confirm that anilinoquinazolines are good starting structures for the next generation of selective drugs against mutant EGFR, whereas CI-1033 and EKB-569 may represent advances for patients with both wild-type and anilinoquinazoline-resistant mutant tumors. 相似文献