全文获取类型
收费全文 | 146篇 |
免费 | 16篇 |
专业分类
162篇 |
出版年
2022年 | 4篇 |
2021年 | 2篇 |
2020年 | 3篇 |
2018年 | 1篇 |
2017年 | 4篇 |
2016年 | 3篇 |
2015年 | 2篇 |
2014年 | 7篇 |
2013年 | 10篇 |
2012年 | 6篇 |
2011年 | 13篇 |
2010年 | 6篇 |
2009年 | 3篇 |
2008年 | 7篇 |
2007年 | 5篇 |
2006年 | 1篇 |
2005年 | 3篇 |
2004年 | 7篇 |
2003年 | 3篇 |
2002年 | 4篇 |
2001年 | 2篇 |
2000年 | 6篇 |
1999年 | 3篇 |
1998年 | 6篇 |
1996年 | 2篇 |
1994年 | 1篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 3篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1977年 | 2篇 |
1975年 | 3篇 |
1973年 | 2篇 |
1972年 | 3篇 |
1971年 | 3篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1967年 | 1篇 |
1964年 | 1篇 |
1963年 | 1篇 |
1948年 | 1篇 |
排序方式: 共有162条查询结果,搜索用时 0 毫秒
51.
Phosphorylation of CREB Ser142 regulates light-induced phase shifts of the circadian clock 总被引:9,自引:0,他引:9
Gau D Lemberger T von Gall C Kretz O Le Minh N Gass P Schmid W Schibler U Korf HW Schütz G 《Neuron》2002,34(2):245-253
Biological rhythms are driven in mammals by a central circadian clock located in the suprachiasmatic nucleus (SCN). Light-induced phase shifting of this clock is correlated with phosphorylation of CREB at Ser133 in the SCN. Here, we characterize phosphorylation of CREB at Ser142 and describe its contribution to the entrainment of the clock. In the SCN, light and glutamate strongly induce CREB Ser142 phosphorylation. To determine the physiological relevance of phosphorylation at Ser142, we generated a mouse mutant, CREB(S142A), lacking this phosphorylation site. Light-induced phase shifts of locomotion and expression of c-Fos and mPer1 in the SCN are significantly attenuated in CREB(S142A) mutants. Our findings provide genetic evidence that CREB Ser142 phosphorylation is involved in the entrainment of the mammalian clock and reveal a novel phosphorylation-dependent regulation of CREB activity. 相似文献
52.
53.
54.
CREB, neurogenesis and depression 总被引:3,自引:0,他引:3
55.
A genome survey of Moniliophthora perniciosa gives new insights into Witches' Broom Disease of cacao
Jorge MC Mondego Marcelo F Carazzolle Gustavo GL Costa Eduardo F Formighieri Lucas P Parizzi Johana Rincones Carolina Cotomacci Dirce M Carraro Anderson F Cunha Helaine Carrer Ramon O Vidal Raíssa C Estrela Odalys García Daniela PT Thomazella Bruno V de Oliveira Acássia BL Pires Carolina S Maria Rio Marcos Renato R Araújo Marcos H de Moraes Luis AB Castro Karina P Gramacho Marilda S Gonçalves José P Moura Neto Aristóteles Góes Neto Luciana V Barbosa Mark J Guiltinan Bryan A Bailey Lyndel W Meinhardt Julio CM Cascardo Gonçalo AG Pereira 《BMC genomics》2008,9(1):1-25
56.
J Gass WC Lee C Cook N Finch C Stetler K Jansen-West J Lewis CD Link R Rademakers A Nykjær L Petrucelli 《Molecular neurodegeneration》2012,7(1):33
ABSTRACT: BACKGROUND: Progranulin (PGRN), a widely secreted growth factor, is involved in multiple biological functions, and mutations located within the PGRN gene (GRN) are a major cause of frontotemporal lobar degeneration with TDP-43-positive inclusions (FLTD-TDP). In light of recent reports suggesting PGRN functions as a protective neurotrophic factor and that sortilin (SORT1) is a neuronal receptor for PGRN, we used a Sort1-deficient (Sort1/) murine primary hippocampal neuron model to investigate whether PGRN's neurotrophic effects are dependent on SORT1. We sought to elucidate this relationship to determine what role SORT1, as a regulator of PGRN levels, plays in modulating PGRN's neurotrophic effects. RESULTS: As the first group to evaluate the effect of PGRN loss in Grn knockout primary neuronal cultures, we show neurite outgrowth and branching are significantly decreased in Grn/ neurons compared to wild-type (WT) neurons. More importantly, we also demonstrate that PGRN overexpression can rescue this phenotype. However, the recovery in outgrowth is not observed following treatment with recombinant PGRN harboring missense mutations p.C139R, p.P248L or p.R432C, indicating that these mutations adversely affect the neurotrophic properties of PGRN. In addition, we also present evidence that cleavage of fulllength PGRN into granulin peptides is required for increased neuronal outgrowth, suggesting that the neurotrophic functions of PGRN are contained within certain granulins. To further characterize the mechanism by which PGRN impacts neuronal morphology, we assessed the involvement of SORT1. We demonstrate that PGRN induced-outgrowth occurs in the absence of SORT1 in Sort1/ cultures. CONCLUSION: We demonstrate that loss of PGRN impairs proper neurite outgrowth and branching, and that exogenous PGRN alleviates this impairment. Furthermore, we determined that exogenous PGRN induces outgrowth independent of SORT1, suggesting another receptor(s) is involved in PGRN induced neuronal outgrowth. 相似文献
57.
S. Mas M. Pagerols P. Gassó A. Ortiz N. Rodriguez A. Morer M. T. Plana A. Lafuente L. Lazaro 《Genes, Brain & Behavior》2014,13(4):409-417
One of the leading biological models of obsessive‐compulsive disorder (OCD) is the frontal‐striatal‐thalamic model. This study undertakes an extensive exploration of the variability in genes related to the regulation of the frontal‐striatal‐thalamic system in a sample of early‐onset OCD trios. To this end, we genotyped 266 single nucleotide polymorphisms (SNPs) in 35 genes in 84 OCD probands and their parents. Finally, 75 complete trios were included in the analysis. Twenty SNPs were overtransmitted from parents to early‐onset OCD probands and presented nominal pointwise P < 0.05 values. Three of these polymorphisms achieved P < 2 × 10?4, the significant P‐value after Bonferroni corrections: rs8190748 and rs992990 localized in GAD2 and rs2000292 in HTR1B. When we stratified our sample according to gender, different trends were observed between males and females. In males, SNP rs2000292 (HTR1B) showed the lowest P‐value (P = 0.0006), whereas the SNPs in GAD2 were only marginally significant (P = 0.01). In contrast, in females HTR1B polymorphisms were not significant, whereas rs8190748 (GAD2) showed the lowest P‐value (P = 0.0006). These results are in agreement with several lines of evidence that indicate a role for the serotonin and γ‐Aminobutyric acid (GABA) pathways in the risk of early‐onset OCD and with the gender differences in OCD pathophysiology reported elsewhere. However, our results need to be replicated in studies with larger cohorts in order to confirm these associations. 相似文献
58.
To analyze autonomic nervous system activity in headache subjects, measurements of heart rate variability (HRV), skin temperature, skin conductance, and respiration were compared to a matched control group. HRV data were recorded in time and frequency domains. Subjects also completed self-report questionnaires assessing psychological distress, fatigue, and sleep dysfunction. Twenty-one headache and nineteen control subjects participated. In the time domain, the number of consecutive R-to-R intervals that varied by more than 50 ms and the standard deviation of the normalized R-to-R intervals, both indices of parasympathetic nervous system activity, were significantly lower in the headache group than the control group. Groups did not differ statistically on HRV measures in the frequency domain. Self-report measures showed significantly increased somatization, hostility, anxiety, symptom distress, fatigue, and sleep problems in the headache group. The results suggest headache subjects have increased sympathetic nervous system activity and decreased parasympathetic activity compared to non-headache control subjects. Headaches subjects also showed greater emotional distress, fatigue, and sleep problems. The results indicate an association between headaches and cardiovascular functioning suggestive of sympathetic nervous system activation in this sample of mixed migraine and tension-type headache sufferers. 相似文献
59.
Scavenger receptor-A mediates gp96/GRP94 and calreticulin internalization by antigen-presenting cells 总被引:7,自引:0,他引:7
Berwin B Hart JP Rice S Gass C Pizzo SV Post SR Nicchitta CV 《The EMBO journal》2003,22(22):6127-6136
gp96 (GRP94) elicits antigen-presenting cell (APC) activation and can direct peptides into the cross- presentation pathways of APC. These responses arise through interactions of gp96 with Toll-like (APC activation) and endocytic (cross-presentation) receptors of APC. Previously, CD91, the alpha2-macroglobulin receptor, was identified as the heat shock/chaperone protein receptor of APC. Recent data indicates, however, that inhibition of CD91 ligand binding does not alter gp96 recognition and uptake. Furthermore, CD91 expression is not itself sufficient for gp96 binding and internalization. We now report that scavenger receptor class-A (SR-A), a prominent scavenger receptor of macrophages and dendritic cells, serves a primary role in gp96 and calreticulin recognition and internalization. gp96 internalization and peptide re-presentation are inhibited by the SR-A inhibitory ligand fucoidin, although fucoidin was without effect on alpha2-macroglobulin binding or uptake. Ectopic expression of SR-A in HEK 293 cells yielded gp96 recognition and uptake activity. In addition, macrophages derived from SR-A-/- mice were substantially impaired in gp96 binding and uptake. These data identify new roles for SR-A in the regulation of cellular responses to heat shock proteins. 相似文献
60.
角质形成细胞生长因子(KGF)在喉粘膜良性、癌前及恶性病变中的mRNA水平分析 总被引:1,自引:0,他引:1
利用原位杂交的方法检测KGFmRNA在正常喉粘膜上皮(N)、慢性非特异性炎症(IF)、不典型增生(DYS)及鳞癌(SCC)中的转录水平,探讨KGF在喉粘膜良性及恶性病变中的分布和可能的作用。结果表明,KGFmRNA不仅在间质中的成纤维细胞中表达,少量的炎细胞及血管内皮细胞中亦表达,而且从N、IF、DYS到SCC、KGFmRNA转录水平逐渐增强;上皮细胞及肿瘤性上皮细胞不表达KGFmRNA,KGFmRNA在分化差的SCC周围间质中表达较分化好的SCC周围间质增多。结论:KGF在上皮与间充质细胞的交互作用中发挥着重要的作用,对维持喉粘膜正常结构、代谢及喉癌的发生发展具有重要意义。 相似文献