全文获取类型
收费全文 | 603篇 |
免费 | 46篇 |
国内免费 | 1篇 |
出版年
2023年 | 4篇 |
2022年 | 9篇 |
2021年 | 31篇 |
2020年 | 12篇 |
2019年 | 22篇 |
2018年 | 18篇 |
2017年 | 18篇 |
2016年 | 20篇 |
2015年 | 43篇 |
2014年 | 45篇 |
2013年 | 40篇 |
2012年 | 52篇 |
2011年 | 52篇 |
2010年 | 34篇 |
2009年 | 26篇 |
2008年 | 28篇 |
2007年 | 32篇 |
2006年 | 27篇 |
2005年 | 18篇 |
2004年 | 24篇 |
2003年 | 16篇 |
2002年 | 21篇 |
2001年 | 6篇 |
2000年 | 6篇 |
1999年 | 4篇 |
1998年 | 6篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1994年 | 4篇 |
1993年 | 3篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1973年 | 1篇 |
1960年 | 1篇 |
1950年 | 1篇 |
排序方式: 共有650条查询结果,搜索用时 406 毫秒
91.
92.
Anne Tarrade Delphine Rousseau-Ralliard Marie-Christine Aubrière Nathalie Peynot Michèle Dahirel Justine Bertrand-Michel Tiphaine Aguirre-Lavin Olivier Morel Nathalie Beaujean Véronique Duranthon Pascale Chavatte-Palmer 《PloS one》2013,8(12)
Maternal environment during early developmental stages plays a seminal role in the establishment of adult phenotype. Using a rabbit model, we previously showed that feeding dams with a diet supplemented with 8% fat and 0.2% cholesterol (HH diet) from the prepubertal period and throughout gestation induced metabolic syndrome in adult offspring. Here, we examined the effects of the HH diet on feto-placental phenotype at 28 days post-coïtum (term = 31days) in relation to earlier effects in the blastocyst (Day 6). At 28 days, both male and female HH fetuses were intrauterine growth retarded and dyslipidemic, with males more affected than females. Lipid droplets accumulated in the HH placentas’ trophoblast, consistent with the increased concentrations in cholesteryl esters (3.2-fold), triacylglycerol (2.5-fold) and stored FA (2.12-fold). Stored FA concentrations were significantly higher in female compared to male HH placentas (2.18-fold, p<0.01), whereas triacylglycerol was increased only in HH males. Trophoblastic lipid droplet accumulation was also observed at the blastocyst stage. The expression of numerous genes involved in lipid pathways differed significantly according to diet both in term placenta and at the blastocyst stage. Among them, the expression of LXR-α in HH placentas was reduced in HH males but not females. These data demonstrate that maternal HH diet affects the blastocyst and induces sex-dependent metabolic adaptations in the placenta, which appears to protect female fetuses from developing severe dyslipidemia. 相似文献
93.
94.
Roselyne Ferrari Isabelle Lacaze Pauline Le Faouder Justine Bertrand-Michel Camille Oger Jean-Marie Galano Thierry Durand Stéphane Moularat Laetitia Chan Ho Tong Charlie Boucher Jaafar Kilani Yohann Petit Océane Vanparis César Trannoy Sylvain Brun Hervé Lalucque Fabienne Malagnac Philippe Silar 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(10):2174-2182
Oxylipins are secondary messengers used universally in the living world for communication and defense. The paradigm is that they are produced enzymatically for the eicosanoids and non-enzymatically for the isoprostanoids. They are supposed to be degraded into volatile organic compounds (VOCs) and to participate in aroma production. Some such chemicals composed of eight carbons are also envisoned as alternatives to fossil fuels. In fungi, oxylipins have been mostly studied in Aspergilli and shown to be involved in signalling asexual versus sexual development, mycotoxin production and interaction with the host for pathogenic species. Through targeted gene deletions of genes encoding oxylipin-producing enzymes and chemical analysis of oxylipins and volatile organic compounds, we show that in the distantly-related ascomycete Podospora anserina, isoprostanoids are likely produced enzymatically. We show the disappearance in the mutants lacking lipoxygenases and cyclooxygenases of the production of 10-hydroxy-octadecadienoic acid and that of 1-octen-3-ol, a common volatile compound. Importantly, this was correlated with the inability of the mutants to repel nematodes as efficiently as the wild type. Overall, our data show that in this fungus, oxylipins are not involved in signalling development but may rather be used directly or as precursors in the production of odors against potential agressors.
Significance
We analyzse the role in inter-kingdom communication of lipoxygenase (lox) and cyclooxygenase (cox) genes in the model fungus Podospora anserina.Through chemical analysis we define the oxylipins and volatile organic compounds (VOCs)produce by wild type and mutants for cox and lox genes,We show that the COX and LOX genes are required for the production of some eight carbon VOCs.We show that COX and LOX genes are involved in the production of chemicals repelling nematodes.This role is very different from the ones previously evidenced in other fungi. 相似文献95.
The mechanism of ω-6 polyunsaturated fatty acid oxidation by wild-type cyclooxygenase 2 and the Y334F variant, lacking a conserved hydrogen bond to the catalytic tyrosyl radical/tyrosine, was examined for the first time under physiologically relevant conditions. The enzymes show apparent bimolecular rate constants and deuterium kinetic isotope effects that increase in proportion to co-substrate concentrations before converging to limiting values. The trends exclude multiple dioxygenase mechanisms as well as the proposal that initial hydrogen atom abstraction from the fatty acid is the first irreversible step in catalysis. Temperature dependent kinetic studies reinforce the novel finding that hydrogen transfer from the reduced catalytic tyrosine to a terminal peroxyl radical is the first irreversible step that controls regio- and stereospecific product formation. 相似文献
96.
The mechanism by which cyclooxygenase-1 (COX-1), a heme- and tyrosyl radical-containing enzyme, catalyzes the regio- and stereospecific oxygenation of polyunsaturated fatty acids to prostaglandin or hydroperoxide products has not been understood. Steady-state kinetic studies conducted with the native substrate arachidonic acid and the slower substrate linoleic acid are described here. Second-order rate constants, kcat/KM for fatty acid and O2, are found to depend upon the concentration of the other cosubstrate. Competitive oxygen kinetic isotope effects (18O KIEs) kcat/KM(16,16O2)/kcat/KM(18,16O2) reveal that a peroxyl radical is formed in or before the first kinetically irreversible step. Together, the results indicate that the oxygenase reaction occurs by a sequential mechanism which most likely involves reversible abstraction of a hydrogen atom from the fatty acid prior to the trapping of the delocalized substrate radical by O2. The identity of the first kinetically irreversible step, subsequent to forming the peroxyl radical, is also discussed in the context of the magnitude of the oxygen kinetic isotope effects as well as the behavior of kcat/KM(O2) in response to changing solvent pH, pD, and viscosity. 相似文献
97.
Kerley-Hamilton JS Pike AM Hutchinson JA Freemantle SJ Spinella MJ 《Biochimica et biophysica acta》2007,1769(4):209-219
The tumor suppressor p53 regulates diverse biological processes primarily via activation of downstream target genes. Even though many p53 target genes have been described, the precise mechanisms of p53 biological actions are uncertain. In previous work we identified by microarray analysis a candidate p53 target gene, FLJ11259/DRAM. In this report we have identified three uncharacterized human proteins with sequence homology to FLJ11259, suggesting that FLJ11259 is a member of a novel family of proteins with six transmembrane domains. Several lines of investigation confirm FLJ11259 is a direct p53 target gene. p53 siRNA prevented cisplatin-mediated up-regulation of FLJ11259 in NT2/D1 cells. Likewise in HCT116 p53+/+ cells and MCF10A cells, FLJ11259 is induced by cisplatin treatment but to a much lesser extent in isogenic p53-suppressed cells. A functional p53 response element was identified 22.3 kb upstream of the first coding exon of FLJ11259 and is shown to be active in reporter assays. In addition, chromatin immunoprecipitation assays indicate that p53 binds directly to this element in vivo and that binding is enhanced following cisplatin treatment. Confocal microscopy showed that an FLJ-GFP fusion protein localizes mainly in a punctate pattern in the cytoplasm. Overexpression studies in Cos-7, Saos2, and NT2/D1 cells suggest that FLJ11259 is associated with increased clonal survival. In summary, we have identified FLJ11259/DRAM as a p53-inducible member of a novel family of transmembrane proteins. FLJ11259/DRAM may be an important modulator of p53 responses in diverse tumor types. 相似文献
98.
Josephine T. Tauer Gustavo Henrique Rigo Canevazzi Justine Schiettekatte-Maltais Frank Rauch Raynald Bergeron Louis-Nicolas Veilleux 《Journal of musculoskeletal & neuronal interactions》2021,21(4):517
Objective:The objective of the current study is to assess the effect of a seven-week voluntary wheel running intervention on muscles and bones properties in a mouse model mimicking dominant severe osteogenesis imperfecta (OI).Methods:Female wild-type (WT) and OI (Col1a1Jrt/+) mice either performed voluntarily wheel-running exercise for 7-weeks or remained sedentary. Running distance and speed, forelimb grip strength, isolated muscle force and fatigability as well as bone morphology and mechanical properties were assessed.Results:We demonstrate that female WT and OI mice voluntarily performed exercise, although OI mice exercised less than WT littermates. The exercise regimen increased soleus muscle masses in WT and OI but increased relative grip strength in WT mice only. Specific muscle force and fatigability were similar between WT and OI mice and did not improve with exercise. Furthermore, the exercise regimen did not improve the femoral architectural and biomechanical properties in OI mice.Conclusion:Our study suggests that voluntary wheel running is not appropriate to assess the effects of exercise in a mouse model of OI. Findings from exercising OI mice model studies may not necessarily be transferable to humans. 相似文献
99.
100.
Justine Chervin Pierre Perio Nathalie Martins-Froment Chiobouaphong Pharkeovilay Karine Reybier Françoise Nepveu Nicolas Fabre Thierry Talou Valérie Bonzon-Ponnet Guillaume Marti 《Metabolomics : Official journal of the Metabolomic Society》2017,13(8):96