全文获取类型
收费全文 | 532篇 |
免费 | 21篇 |
出版年
2024年 | 1篇 |
2023年 | 3篇 |
2022年 | 7篇 |
2021年 | 15篇 |
2020年 | 9篇 |
2019年 | 12篇 |
2018年 | 8篇 |
2017年 | 7篇 |
2016年 | 8篇 |
2015年 | 17篇 |
2014年 | 23篇 |
2013年 | 36篇 |
2012年 | 44篇 |
2011年 | 59篇 |
2010年 | 35篇 |
2009年 | 22篇 |
2008年 | 39篇 |
2007年 | 40篇 |
2006年 | 24篇 |
2005年 | 21篇 |
2004年 | 19篇 |
2003年 | 18篇 |
2002年 | 17篇 |
2001年 | 6篇 |
2000年 | 4篇 |
1999年 | 6篇 |
1998年 | 4篇 |
1997年 | 5篇 |
1996年 | 1篇 |
1995年 | 4篇 |
1994年 | 1篇 |
1992年 | 1篇 |
1990年 | 6篇 |
1989年 | 3篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1979年 | 4篇 |
1978年 | 10篇 |
排序方式: 共有553条查询结果,搜索用时 15 毫秒
101.
Laoui D Movahedi K Van Overmeire E Van den Bossche J Schouppe E Mommer C Nikolaou A Morias Y De Baetselier P Van Ginderachter JA 《The International journal of developmental biology》2011,55(7-9):861-867
Macrophages display remarkable plasticity, allowing these cells to adapt to changing microenvironments and perform functions as diverse as tissue development and homeostasis, inflammation, pathogen clearance and wound healing. Macrophage activation can be triggered by Th1 cytokines and pathogen-associated or endogenous danger signals, leading to the formation of classically activated or M1 macrophages. On the other hand, anti-inflammatory mediators, including IL-4, IL-10, TGF-β and M-CSF, induce diverse anti-inflammatory types of macrophages, known under the generic term M2. In human breast carcinomas, tumor-associated macrophage (TAM) density correlates with poor prognosis. In mouse models of breast cancer, eliminating macrophages from the tumor site, either via genetic or therapeutic means, results in retarded tumor progression. Over the years, multiple signals from the mammary tumor microenvironment have been reported to influence the TAM phenotype and TAM have been propagated as anti-inflammatory M2-like cells. Recent developments point to the existence of at least two distinct TAM subpopulations in mammary tumors, based on a differential expression of markers such as CD206 or MHC II and different in vivo behaviour: perivascular, migratory TAM which are less M2-like, and sessile TAM found at tumor-stroma borders and/or hypoxic regions that resemble more M2-like or "trophic" macrophages. Hence, a further refinement of the molecular and functional heterogeneity of TAM is an avenue for further research, with a potential impact on the usefulness of these cells as therapeutic targets. 相似文献
102.
Nutritionally important PUFAs (polyunsaturated fatty acids) mediate some of their bioactivities through formation of oxygenated metabolites. These bioactive lipids are formed by COX (cyclo-oxygenase), LOX (lipoxygenase) and cytochrome-P450-catalysed reactions, as well as non-enzymatic lipid peroxidation. These reactions produce numerous species, some of which can be formed through more than one pathway. MS-based lipidomics offers the selectivity and sensitivity required for qualitative and quantitative analysis of multiple lipid species, in a variety of biological systems, and can facilitate the study of these mediators. 相似文献
103.
Papanastasiou SA Diamantidis AD Nakas CT Carey JR Papadopoulos NT 《Journal of insect physiology》2011,57(10):1368-1374
Although age-based effects on the reproductive success of males have been reported in several animal taxa the cost of aging on male mating success in lekking species has not been fully explored. We used the Mediterranean fruit fly, a lekking species, to investigate possible cost of aging on male reproductive success. We performed no choice and choice mating tests to test the hypothesis that aging does not affect the mating performance (mating success in conditions lacking competition) or the mating competitiveness (mating success against younger rivals) of males. The mating probability of older males decreased significantly when competing with younger males. Aging gradually reduced the mating performance of males but older males were still accepted as mating partners in conditions lacking competition. Therefore, older males are capable of performing the complete repertoire of sexual performance but fail to be chosen by females in the presence of young rivals. Older males achieved shorter copulations than younger ones, and female readiness to mate was negatively affected by male age. Older and younger males transferred similar amount of spermatozoids to female spermathecae. Females stored spermatozoids asymmetrically in the two spermathecae regardless the age of their mating partner. Aging positively affected the amount of spermatozoids in testes of both mated and nonmated males. No significant differences were observed on the amount of spermatozoids between mated and nonmated males. 相似文献
104.
Georgakilas AG 《Mutation research》2011,711(1-2):1-2
Knowledge of the chemistry behind induction of DNA damage and processing mechanisms is considered very important not only for the understanding of the biological significance but also for clinical applications. In this Special Issue, we have compiled a number of succinct reviews and original research articles, by top experts in their fields. The articles discuss and/or explore the current status of knowledge and new advances in the chemical and molecular pathways related to the induction of high oxidative stress, DNA damage and its repair in human cells and tissues. Experimental and theoretical insights are provided of how the DNA repair processes maybe modulated by gene mutations and other factors like temperature and radiation quality. 相似文献
105.
Mikelis C Lamprou M Koutsioumpa M Koutsioubas AG Spyranti Z Zompra AA Spiliopoulos N Vradis AA Katsoris P Spyroulias GA Cordopatis P Courty J Papadimitriou E 《Journal of cellular biochemistry》2011,112(6):1532-1543
Pleiotrophin (PTN) is a heparin-binding growth factor that plays a significant role in tumor growth and angiogenesis. We have previously shown that in order for PTN to induce migration of endothelial cells, binding to both α(ν) β(3) integrin and its receptor protein tyrosine phosphatase beta/zeta (RPTPβ/ζ) is required. In the present study we show that a synthetic peptide corresponding to the last 25 amino acids of the C-terminal region of PTN (PTN(112-136) ) inhibited angiogenesis in the in vivo chicken embryo chorioallantoic membrane (CAM) assay and PTN-induced migration and tube formation of human endothelial cells in vitro. PTN(112-136) inhibited binding of PTN to α(ν) β(3) integrin, and as shown by surface plasmon resonance (SPR) measurements, specifically interacted with the specificity loop of the extracellular domain of β(3) . Moreover, it abolished PTN-induced FAK Y397 phosphorylation, similarly to the effect of a neutralizing α(ν) β(3) -selective antibody. PTN(112-136) did not affect binding of PTN to RPTPβ/ζ in endothelial cells and induced β(3) Y773 phosphorylation and ERK1/2 activation to a similar extent with PTN. This effect was inhibited by down-regulation of RPTPβ/ζ by siRNA or by c-src inhibition, suggesting that PTN(112-136) may interact with RPTPβ/ζ. NMR spectroscopy studies showed that PTN(112-136) was characterized by conformational flexibility and absence of any element of secondary structure at room temperature, although the biologically active peptide segment 123-132 may adopt a defined structure at lower temperature. Collectively, our data suggest that although PTN(112-136) induces some of the signaling pathways triggered by PTN, it inhibits PTN-induced angiogenic activities through inhibition of PTN binding to α(ν) β(3) integrin. 相似文献
106.
Dorothea Haas Hongying Gan-Schreier Claus-Dieter Langhans Alexandros Anninos Gisela Haege Peter Burgard Andreas Schulze Georg F. Hoffmann Jürgen G. Okun 《Gene》2014
Biochemical detection of inborn errors of creatine metabolism or transport relies on the analysis of three main metabolites in biological fluids: guanidinoacetate (GAA), creatine (CT) and creatinine (CTN). Unspecific clinical presentation of the diseases might be the cause that only few patients have been diagnosed so far. We describe a LC–MS/MS method allowing fast and reliable diagnosis by simultaneous quantification of GAA, CT and CTN in urine, plasma and cerebrospinal fluid (CSF) and established reference values for each material. 相似文献
107.
Alexandros Goulas Matteo Bastiani Gleb Bezgin Harry B. M. Uylings Alard Roebroeck Peter Stiers 《PLoS computational biology》2014,10(3)
The macaque brain serves as a model for the human brain, but its suitability is challenged by unique human features, including connectivity reconfigurations, which emerged during primate evolution. We perform a quantitative comparative analysis of the whole brain macroscale structural connectivity of the two species. Our findings suggest that the human and macaque brain as a whole are similarly wired. A region-wise analysis reveals many interspecies similarities of connectivity patterns, but also lack thereof, primarily involving cingulate regions. We unravel a common structural backbone in both species involving a highly overlapping set of regions. This structural backbone, important for mediating information across the brain, seems to constitute a feature of the primate brain persevering evolution. Our findings illustrate novel evolutionary aspects at the macroscale connectivity level and offer a quantitative translational bridge between macaque and human research. 相似文献
108.
109.
Sfikas A Batsi C Tselikou E Vartholomatos G Monokrousos N Pappas P Christoforidis S Tzavaras T Kanavaros P Gorgoulis VG Marcu KB Kolettas E 《Cellular signalling》2012,24(11):2007-2023
DNA damage responses (DDR) invoke senescence or apoptosis depending on stimulus intensity and the degree of activation of the p53-p21(Cip1/Waf1) axis; but the functional impact of NF-κB signaling on these different outcomes in normal vs. human cancer cells remains poorly understood. We investigated the NF-κB-dependent effects and mechanism underlying reactive oxygen species (ROS)-mediated DDR outcomes of normal human lung fibroblasts (HDFs) and A549 human lung cancer epithelial cells. To activate DDR, ROS accumulation was induced by different doses of H(2)O(2). The effect of ROS induction caused a G2 or G2-M phase cell cycle arrest of both human cell types. However, ROS-mediated DDR eventually culminated in different end points with HDFs undergoing premature senescence and A549 cancer cells succumbing to apoptosis. NF-κB p65/RelA nuclear translocation and Ser536 phosphorylation were induced in response to H(2)O(2)-mediated ROS accumulation. Importantly, blocking the activities of canonical NF-κB subunits with an IκBα super-repressor or suppressing canonical NF-κB signaling by IKKβ knock-down accelerated HDF premature senescence by up-regulating the p53-p21(Cip1/Waf1) axis; but inhibiting the canonical NF-κB pathway exacerbated H(2)O(2)-induced A549 cell apoptosis. HDF premature aging occurred in conjunction with γ-H2AX chromatin deposition, senescence-associated heterochromatic foci and beta-galactosidase staining. p53 knock-down abrogated H(2)O(2)-induced premature senescence of vector control- and IκBαSR-expressing HDFs functionally linking canonical NF-κB-dependent control of p53 levels to ROS-induced HDF senescence. We conclude that IKKβ-driven canonical NF-κB signaling has different functional roles for the outcome of ROS responses in the contexts of normal vs. human tumor cells by respectively protecting them against DDR-dependent premature senescence and apoptosis. 相似文献
110.
The effects of lipoxin A and lipoxin B on functional responses of human granulocytes 总被引:2,自引:0,他引:2
J Palmblad H Gyllenhammar B Ringertz C N Serhan B Samuelsson K C Nicolaou 《Biochemical and biophysical research communications》1987,145(1):168-175
Lipoxin A and lipoxin B (LXA and LXB) are formed from arachidonic acid by leukocyte 5- and 15-lipoxygenases. We have assessed the effects of synthetic lipoxins on functional responses of human granulocytes. LXA stimulated migration at 1 nM. The effect was highly stereospecific, since e.g. 6S-LXA and LXB were less active than LXA. Neither synthetic LXA nor several of its stereoisomers provoked degranulation or aggregation. LXB and its isomers did not induce any of these functional responses. These results indicate that migratory granulocyte responses to LXA are highly stereospecific. 相似文献