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61.
Carine Chavey Gwendal Lazennec Sylviane Lagarrigue Cyrielle Clapé Irena Iankova Jacques Teyssier Jean-Sébastien Annicotte Julien Schmidt Chikage Mataki Hiroyasu Yamamoto Rosario Sanches Anna Guma Vladimir Stich Michaela Vitkova Bénédicte Jardin-Watelet Eric Renard Robert Strieter Antoinette Tuthill Gôkhan S. Hotamisligil Antonio Vidal-Puig Lluis Fajas 《Cell metabolism》2009,9(4):339-349
62.
Carmen Doñate Joan Carles Balasch Agnes Callol Julien Bobe Lluis Tort Simon MacKenzie 《Marine biotechnology (New York, N.Y.)》2010,12(1):88-99
Immunostimulant-containing diets are commonly used in aquaculture to enhance the resistance of cultured fish to disease and
stress. Although widespread in use, there have been conflicting results published, and surprisingly little is known about
the regulation of immune response-related genes in tissues key to mucosal immunity induced by immunostimulant dietary feeding.
Using a salmonid-specific microarray platform enriched with immune-related genes and in situ hybridization, we investigated
dietary acclimation in two organs relevant to mucosal immunity, the gills and the intestine, in the rainbow trout (Oncorhynchus mykiss). Immunostimulant diets significantly changed gene expression profiles and gene distribution in a tissue-specific manner:
genes and functional Gene Ontology categories involved in immunity were differently expressed at portals of entry where significant
changes in genes and functional groups related to remodeling processes and antigen presentation were observed. Furthermore,
genes involved in chemotaxis, cell differentiation, antigen-presenting capacity and tissue remodeling were localized in both
organs. 相似文献
63.
Background
Regulatory T-cells (Tregs), characterized as CD4+CD25hi T-cells expressing FOXP3, play a crucial role in controlling healthy immune development during early immune maturation. Recently, FOXP3 demethylation was suggested to be a novel marker for natural Tregs in adults. In cord blood, the role and function of Tregs and its demethylation is poorly understood. We assessed FOXP3 demethylation in cord blood in relation to previously used Treg markers such as CD4+CD25hi, FOXP3 mRNA, protein expression, and suppressive Treg function.Methodology
Cord blood mononuclear cells (CBMC) were isolated from 70 healthy neonates, stimulated for 3 days with the microbial stimulus lipid A (LpA), and allergen Dermatophagoides pteronyssinus (Derp1). Tregs (CD4+CD25hi, intracellular, mRNA FOXP3 expression, isolated cells), DNA methylation of the FOXP3-locus and suppressive Treg function were assessed.Principal Findings
Demethylation of FOXP3 in whole blood was specific for isolated CD4+CD25hi Tregs. Demethylation of FOXP3 was positively correlated with unstimulated and LpA-stimulated FOXP3 mRNA-expression (p≤0.05), and CD4+CD25hi T-cells (p≤0.03). Importantly, increased FOXP3 demethylation correlated with more efficient suppressive capacity of Tregs (r = 0.72, p = 0.005). Furthermore, FOXP3 demethylation was positively correlated with Th2 cytokines (IL-5, IL-13) following LpA-stimulation (p = 0.006/0.04), with Th2 and IL-17 following Derp1+LpA-stimulations (p≤0.009), but not Th1 cytokines (IFN-γ).Conclusions
FOXP3 demethylation reliable quantifies Tregs in cord blood. FOXP3 demethylation corresponds well with the suppressive potential of Tregs. The resulting strict correlation with functionally suppressive Tregs and the relative ease of measurement render it into a valuable novel marker for large field studies assessing Tregs as qualitative marker indicative of functional activity. 相似文献64.
Heyer E Brazier L Ségurel L Hegay T Austerlitz F Quintana-Murci L Georges M Pasquet P Veuille M 《Human biology; an international record of research》2011,83(3):379-392
The aim of the present study is to document the evolution of the lactase persistence trait in Central Asia, a geographical area that is thought to have been a region of long-term pastoralism. Several ethnic groups co-exist in this area: Indo-Iranian speakers who are traditionally agriculturist (Tajik) and Turkic speakers who used to be nomadic herders (Kazakh, Karakalpak, Kyrgyz, Turkmen). It was recently demonstrated that horse milking practice existed in the Botai culture of Kazakhstan as early as 5,500 BP ( Outram et al. 2009 ). However, the frequency of the lactase persistence trait and its genetic basis in Central Asian populations remain largely unknown. We propose here the first genotype-phenotype study of lactase persistence in Central Asia based on 183 individuals, as well as the estimation of the time of expansion of the lactase-persistence associated polymorphism. Our results show a remarkable genetic-phenotypic correlation, with the causal polymorphism being the same than in Europe (-13.910C>T, rs4988235). The lactase persistence trait is at low frequency in these populations: between 25% and 32% in the Kazakh population (traditionally herders), according to phenotype used, and between 11% and 30% in the Tajiko-Uzbek population (agriculturalists). The difference in lactase persistence between populations, even if small, is significant when using individuals concordant for both excretion of breath hydrogen and the lactose tolerance blood glucose test phenotypes (P = 0.018, 25% for Kazakh vs. 11% for Tajiko-Uzbeks), and the difference in frequency of the -13.910*T allele is almost significant (P = 0.06, 30% for Kazakhs vs. 19% for Tajiko-Uzbeks). Using the surrounding haplotype, we estimate a date of expansion of the T allele around 6,000-12,000 yrs ago, which is consistent with archaeological records for the emergence of agropastoralism and pastoralism in Central Asia. 相似文献
65.
Irene Bianconi Lluis Sempere Patima Permpoonpattana Karen Smith Marcin Dembek Sisareuth Tan Marie‐Clémence Brisson Alain R. Brisson Neil F. Fairweather Simon M. Cutting 《Molecular microbiology》2014,92(5):1025-1038
The BclA protein is a major component of the outermost layer of spores of a number of bacterial species and Clostridium difficile carries three bclA genes. Using insertional mutagenesis each gene was characterized and spores devoid of these proteins had surface aberrations, reduced hydrophobicity and germinated faster than wild‐type spores. Therefore the BclA proteins were likely major components of the spore surface and when absent impaired the protective shield effect of this outermost layer. Analysis of infection and colonization in mice and hamsters revealed that the 50% infectious dose (ID50) of spores was significantly higher (2‐logs) in the bclA1? mutant compared to the isogenic wild‐type control, but that levels of toxins (A and B) were indistinguishable from animals dosed with wild‐type spores. bclA1? spores germinated faster than wild‐type spores yet mice were less susceptible to infection suggesting that BclA1 must play a key role in the initial (i.e. pre‐spore germination) stages of infection. We also show that the ID50 was higher in mice infected with R20291, a ‘hypervirulent’ 027 strain, that carries a truncated BclA1 protein. 相似文献
66.
Xiangyu Zhou Lluis Cordon-Barris Tinatin Zurashvili 《Cell cycle (Georgetown, Tex.)》2014,13(20):3164-3168
The PI3K/PDK1/PKB signaling pathway plays essential roles in regulating neuronal survival, differentiation and plasticity in response to neurotrophic factors, neurotransmitters and ion channels. Both PDK1 and PKB can interact at the plasma membrane with a phosphoinositide synthesized by PI3K, the second messenger PtdIns(3,4,5)P3, enabling PDK1 to phosphorylate and activate PKB. In the PDK1 K465E knock-in mice expressing a mutant form of PDK1 incapable of phosphoinositide binding, activation of PKB was markedly affected, but not totally abolished. It has been recently proposed that in the absence of PtdIns(3,4,5)P3 binding, PDK1 can still moderately activate PKB due to a docking site-mediated interaction of these 2 kinases. A recent report has uncovered that in the PDK1 K465E mice neurons, a PKB signal threshold was sufficient to support neuronal survival responses, whereas neuritogenesis, neuronal polarization and axon outgrowth were severely impaired. We propose here that the low-efficiency mechanism of PKB activation observed in the PDK1 K465E mice might represent the ancestral mechanism responsible for the essential functions of this pathway, while the phosphoinositide-dependent activation should be considered an evolutionary innovation that enabled the acquisition of novel functions. 相似文献
67.
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69.
Maria José Ramírez-Bajo Pedro de Atauri Fernando Ortega Hans V. Westerhoff Josep Lluis Gelpí Josep J. Centelles Marta Cascante 《PloS one》2014,9(1)
The effects of pre-incubation with mercury (Hg2+) and cadmium (Cd2+) on the activities of individual glycolytic enzymes, on the flux and on internal metabolite concentrations of the upper part of glycolysis were investigated in mouse muscle extracts. In the range of metal concentrations analysed we found that only hexokinase and phosphofructokinase, the enzymes that shared the control of the flux, were inhibited by Hg2+ and Cd2+. The concentrations of the internal metabolites glucose-6-phosphate and fructose-6-phosphate did not change significantly when Hg2+ and Cd2+ were added. A mathematical model was constructed to explore the mechanisms of inhibition of Hg2+ and Cd2+ on hexokinase and phosphofructokinase. Equations derived from detailed mechanistic models for each inhibition were fitted to the experimental data. In a concentration-dependent manner these equations describe the observed inhibition of enzyme activity. Under the conditions analysed, the integral model showed that the simultaneous inhibition of hexokinase and phosphofructokinase explains the observation that the concentrations of glucose-6-phosphate and fructose-6-phosphate did not change as the heavy metals decreased the glycolytic flux. 相似文献
70.
Helmut Schr?der Lourdes Ribas Corinna Koebnick Anna Funtikova Santiago F. Gomez Montserat Fíto Carmen Perez-Rodrigo Lluis Serra-Majem 《PloS one》2014,9(1)