全文获取类型
收费全文 | 232篇 |
免费 | 15篇 |
专业分类
247篇 |
出版年
2023年 | 2篇 |
2022年 | 2篇 |
2021年 | 9篇 |
2020年 | 6篇 |
2019年 | 3篇 |
2018年 | 5篇 |
2017年 | 8篇 |
2016年 | 10篇 |
2015年 | 7篇 |
2014年 | 12篇 |
2013年 | 8篇 |
2012年 | 23篇 |
2011年 | 16篇 |
2010年 | 13篇 |
2009年 | 19篇 |
2008年 | 12篇 |
2007年 | 9篇 |
2006年 | 14篇 |
2005年 | 7篇 |
2004年 | 12篇 |
2003年 | 11篇 |
2002年 | 15篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1999年 | 5篇 |
1998年 | 2篇 |
1997年 | 3篇 |
1994年 | 2篇 |
1992年 | 2篇 |
1989年 | 1篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1982年 | 1篇 |
1980年 | 1篇 |
排序方式: 共有247条查询结果,搜索用时 15 毫秒
101.
Jere Tolvanen Sami M. Kivelä Blandine Doligez Jennifer Morinay Lars Gustafsson Piter Bijma Veli-Matti Pakanen Jukka T. Forsman 《Evolution; international journal of organic evolution》2020,74(10):2332-2347
Social information use for decision-making is common and affects ecological and evolutionary processes, including social aggregation, species coexistence, and cultural evolution. Despite increasing ecological knowledge on social information use, very little is known about its genetic basis and therefore its evolutionary potential. Genetic variation in a trait affecting an individual's social and nonsocial environment may have important implications for population dynamics, interspecific interactions, and, for expression of other, environmentally plastic traits. We estimated repeatability, additive genetic variance, and heritability of the use of conspecific and heterospecific social cues (abundance and breeding success) for breeding site choice in a population of wild collared flycatchers Ficedula albicollis. Repeatability was found for two social cues: previous year conspecific breeding success and previous year heterospecific abundance. Yet, additive genetic variances for these two social cues, and thus heritabilities, were low. This suggests that most of the phenotypic variation in the use of social cues and resulting conspecific and heterospecific social environment experienced by individuals in this population stems from phenotypic plasticity. Given the important role of social information use on ecological and evolutionary processes, more studies on genetic versus environmental determinism of social information use are needed. 相似文献
102.
The effect of human chorionic gonadotropin (hCG) on in vitro progesterone (P) level in the uterus was investigated by using short-term incubations of uterine tissue taken from 4-day cyclic rats at different stages of the estrous cycle. Control incubations resulted in a decrease of endogenous P content in uteri removed from rats in proestrus (PRO), estrus (EST), and metestrus (MET): -25% (n = 6), -60% (n = 6), and -45% (n = 8), respectively. The amount of P found after incubation of MET tissue in the presence of hCG was significantly higher (p less than 0.001) than that found after control incubations. The hCG effect was dose-dependent and was not observed with PRO or EST tissue. Although the mean P level found in MET tissue after incubation with 10 IU/ml hCG was not significantly different from the mean level found in unincubated tissue (1562 +/- 341 vs. 1470 +/- 174 pg/mg protein, n = 8), an obvious synthesis was observed in two experiments. It thus seems likely that observed hCG effect would involve a de novo P synthesis rather than a decrease of P catabolism. Furthermore, hCG induced a dose-dependent increase of cyclic adenosine 3', 5'-monophosphate (cAMP) uterine levels in MET tissue. N,O'-dibutyryl cyclic AMP [Bu)2 cAMP) at 5 mM induced a significative increase (p less than 0.01) of P uterine level in EST and MET tissue compared to control incubations, but had no effect on PRO tissue. Our results suggest the progressive maturation throughout the rat estrous cycle of a luteinizing hormone/hCG- and cAMP-dependent process able to regulate uterine P content.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
103.
Cécile Gladine Monika Zmojdzian Laurie Joumard-Cubizolles Marie-Anne Verny Blandine Comte Andrzej Mazur 《Genes & nutrition》2014,9(5)
The omega-3 fatty acid docosahexaenoic acid (DHA) has potent anti-atherogenic properties but its mechanisms of action at the vascular level remain poorly explored. Knowing the broad range of molecular targets of omega-3 fatty acids, microarray analysis was used to open-mindedly evaluate the effects of DHA on aorta gene expression in LDLR−/− mice and better understand its local anti-atherogenic action. Mice were fed an atherogenic diet and received daily oral gavages with oils rich in oleic acid or DHA. Bioinformatics analysis of microarray data first identified inflammation and innate immunity as processes the most affected by DHA supplementation within aorta. More precisely, several down-regulated genes were associated with the inflammatory functions of macrophages (e.g., CCL5 and CCR7), cell movement (e.g., ICAM-2, SELP, and PECAM-1), and the major histocompatibility complex (e.g., HLA-DQA1 and HLA-DRB1). Interestingly, several genes were identified as specific biomarkers of macrophage polarization, and their changes suggested a preferential orientation toward a M2 reparative phenotype. This observation was supported by the upstream regulator analysis highlighting the involvement of three main regulators of macrophage polarization, namely PPARγ (z-score = 2.367, p = 1.50 × 10−13), INFγ (z-score = −2.797, p = 2.81 × 10−14), and NFκB (z-score = 2.360, p = 6.32 × 10−9). Moreover, immunohistological analysis of aortic root revealed an increased abundance of Arg1 (+111 %, p = 0.01), a specific biomarker of M2 macrophage. The present study showed for the first time that DHA supplementation during atherogenesis is associated with protective modulation of inflammation and innate immunity pathways within aorta putatively through the orientation of plaque macrophages toward a M2 reparative phenotype.
Electronic supplementary material
The online version of this article (doi:10.1007/s12263-014-0424-4) contains supplementary material, which is available to authorized users. 相似文献104.
Barbara Tschirren Erik Postma Lars Gustafsson Ton G. G. Groothuis Blandine Doligez 《Ecology letters》2014,17(10):1310-1315
Maternal hormones are important mediators of prenatal maternal effects. Although many experimental studies have demonstrated their potency in shaping offspring phenotypes, we know remarkably little about their adaptive value. Using long‐term data on a wild collared flycatcher (Ficedula albicollis) population, we show that natural selection acts in opposite ways on two maternally derived androgens, yolk androstenedione (A4) and yolk testosterone (T). High yolk A4 concentrations are associated with higher fitness, whereas high yolk T concentrations are associated with lower fitness. Natural selection thus favours females that produce eggs with high A4 and low T concentrations. Importantly, however, there exists a positive (non‐genetic) correlation between A4 and T, which suggests that females are limited in their ability to reach this adaptive optimum. Thereby, these results provide strong evidence for an adaptive value of differential maternal androgen deposition, and a mechanistic explanation for the maintenance of variation in maternal investment in the wild. 相似文献
105.
106.
In the present study, we show that lethal toxin from Clostridium sordellii (TcsL-82) activates the three MAP kinase pathways, but that only a permeable and specific c-Jun-NH2-terminal kinase (JNK) inhibitor, JNK inhibitor II, prevents toxin-dependent actin depolymerization and cell rounding. We show that JNK activation is dependent on entry of the toxin N-terminal domain into the cytosol as bafilomycin A1, which prevents acidification of endocytic vesicle and subsequent cytosolic translocation of the toxin N-terminal domain, prevents JNK activation. Inhibition of JNK activity delays small GTPase glucosylation generated by N-terminal domain catalytic activity. Using a cell line mutant deficient in UDP-glucose, we observed that activation of JNK occurs even in the absence of small GTPase glucosylation and, thus, is independent of the toxin intrinsic catalytic activity. Facilitation of target glucosylation by JNK activation appeared to be restricted to TcsL-82 and was not a general feature of large clostridial toxins. Indeed, it was not observed with Toxin B from Clostridium difficile although this toxin also activates JNK. 相似文献
107.
Naimi A Martinez AS Specq ML Mrac A Diss B Mathieu M Sourdaine P 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2009,152(2):189-196
The Pacific oyster Crassostrea gigas is a successive not systematic protandric hermaphrodite. Searching for an ortholog to Dmrt1, a conserved sex determinism factor, we have identified the first complete cDNA of a DM factor in Lophotrochozoa which we have called Cg-DMl (Crassostrea gigas DMRT-like). It is 359aa long, with the DM domain common to all the family factors, and one DMA domain specific to members such as Dmrt4 and Dmrt5. Its gene presents one intron of 598 bp. Real time PCR and in situ hybridization have shown that Cg-DMl was expressed in both sexes, with a significantly higher expression in male than in female gonads at the end of the adult gametogenetic cycle and that a significant peak of expression was observed in spat between 1 and 2 months of age. These results suggest that Cg-DMl may be involved in the development of the gonad and may constitute preliminary clues for future work in order to better understand DM protein evolution. 相似文献
108.
Chaperoning of insertion of membrane proteins into lipid bilayers by hemifluorinated surfactants: application to diphtheria toxin 总被引:2,自引:0,他引:2
Palchevskyy SS Posokhov YO Olivier B Popot JL Pucci B Ladokhin AS 《Biochemistry》2006,45(8):2629-2635
Hemifluorinated compounds, such as HF-TAC, make up a novel class of nondetergent surfactants designed to keep membrane proteins soluble under nondissociating conditions [Breyton, C., et al. (2004) FEBS Lett. 564, 312]. Because fluorinated and hydrogenated chains do not mix well, supramicellar concentrations of these surfactants can coexist with intact lipid vesicles. To test the ability of HF-TAC to assist proper membrane insertion of proteins, we examined its effect on the pH-triggered insertion of the diphtheria toxin T-domain. The function of the T-domain is to translocate the catalytic domain across the lipid bilayer in response to acidification of the endosome. This translocation is accompanied by the formation of a pore, which we used as a measure of activity in a vesicle leakage assay. We have also used F?rster resonance energy transfer to follow the effect of HF-TAC on aggregation of aqueous and membrane-bound T-domain. Our data indicate that the pore-forming activity of the T-domain is affected by the dynamic interplay of two principal processes: productive pH-triggered membrane insertion and nonproductive aggregation of the aqueous T-domain at low pH. The presence of HF-TAC in the buffer is demonstrated to suppress aggregation in solution and ensure correct insertion and folding of the T-domain into the lipid vesicles, without solubilizing the latter. Thus, hemifluorinated surfactants stabilize the low-pH conformation of the T-domain as a water-soluble monomer while acting as low-molecular weight chaperones for its insertion into preformed lipid bilayers. 相似文献
109.
Caixàs A Giménez-Palop O Giménez-Pérez G Potau N Berlanga E González-Glemente JM Arroyo J Laferrère B Mauricio D 《Hormone research》2006,65(1):39-45
AIM: To investigate fasting and postprandial adiponectin levels in PWS patients as compared to obese and lean subjects and whether they could contribute to the pathogenesis of obesity in this syndrome. METHODS: We studied 7 patients with PWS, 16 obese patients and 42 lean subjects for the fasting study. From this group, we evaluated 7 patients with PWS, 7 age-sex-BMI-matched obese non-PWS patients and 7 age-sex-matched lean subjects before and after the administration of 3,139.5 kJ (750 kcal) of a standard liquid meal (53.2% carbohydrate, 30% fat, 16.7% protein) after an overnight fast. Blood samples were obtained every 15 min for the first hour and every 30 min thereafter until 6 h. Adiponectin, IGF-I, glucose, triglycerides, cholesterol, and insulin were measured. RESULTS: Fasting plasma adiponectin levels were lower in PWS than in lean subjects (5.24+/-2.56 vs. 8.28+/-4.63 microg/ml, p=0.041) but higher than in obese patients (4.01+/-1.27 microg/ml, p=0.047). After the meal, adiponectin concentrations mildly decreased in PWS at time point 240 min, while in obese and lean subjects no changes were observed. However, 6-hour postprandial AUC for adiponectin was similar in all three groups. CONCLUSION: Fasting adiponectin levels are low in PWS, but they are so mildly modulated postprandially that these changes do not seem significant for the pathogenesis of obesity in this syndrome. 相似文献
110.
This protocol describes a methodology for the genetic transformation of the rodent malaria parasite Plasmodium berghei and the subsequent selection of transformed parasites expressing green fluorescent protein (GFP) by flow-sorting. It provides methods for: transfection of the schizont stage with DNA constructs that contain gfp as the selectable marker; selection of fluorescent mutants by flow-sorting; and injection of flow-sorted, GFP-expressing parasites into mice and the subsequent collection of transformed parasites. The use of two different promoters for the expression of GFP is described; these two promoters require slightly different procedures for the selection of mutants. The protocol enables the collection of transformed parasites within 10-12 days after transfection. The genetic modification of P. berghei is widely used to investigate gene function in Plasmodium sp. The application of flow-sorting to the selection of transformed parasites increases the possibilities of parasite mutagenesis, by effectively expanding the range of selectable markers. 相似文献