全文获取类型
收费全文 | 1027篇 |
免费 | 51篇 |
国内免费 | 26篇 |
出版年
2024年 | 2篇 |
2023年 | 12篇 |
2022年 | 18篇 |
2021年 | 43篇 |
2020年 | 18篇 |
2019年 | 28篇 |
2018年 | 34篇 |
2017年 | 13篇 |
2016年 | 25篇 |
2015年 | 25篇 |
2014年 | 65篇 |
2013年 | 111篇 |
2012年 | 45篇 |
2011年 | 47篇 |
2010年 | 70篇 |
2009年 | 40篇 |
2008年 | 51篇 |
2007年 | 51篇 |
2006年 | 45篇 |
2005年 | 51篇 |
2004年 | 25篇 |
2003年 | 38篇 |
2002年 | 30篇 |
2001年 | 28篇 |
2000年 | 18篇 |
1999年 | 19篇 |
1998年 | 21篇 |
1997年 | 20篇 |
1996年 | 14篇 |
1995年 | 8篇 |
1994年 | 19篇 |
1993年 | 18篇 |
1992年 | 9篇 |
1991年 | 8篇 |
1990年 | 14篇 |
1989年 | 5篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 5篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1973年 | 1篇 |
排序方式: 共有1104条查询结果,搜索用时 31 毫秒
91.
Barbara S Bregman 《Current opinion in neurobiology》1998,8(6):800-807
Important advances have been made in our understanding of conditions that influence the intrinsic capacity of mature CNS neurons to initiate and maintain a regrowth response. The combination of exogenous neurotrophic support with strategies to alter the terrain at the injury site itself suggests that there are important interactions between them that lead to increased axonal regeneration. The ability of chronically injured neurons to initiate a regeneration response is unexpected. Our view of the role that inhibitors play in restricting axonal growth has also expanded. The findings indicate that the windows of opportunity for enhancing growth after spinal cord injury may be more numerous than previously thought. 相似文献
92.
Kun Gao Yuan Chi Xiling Zhang Hui Zhang Gang Li Wei Sun Masayuki Takeda Jian Yao 《Journal of cellular and molecular medicine》2015,19(10):2469-2480
Gap junctions (GJs) play an important role in the regulation of cell response to many drugs. However, little is known about their mechanisms. Using an in vitro model of cytotoxicity induced by geneticin (G418), we explored the potential signalling mechanisms involved. Incubation of cells with G418 resulted in cell death, as indicated by the change in cell morphology, loss of cell viability and activation of caspase‐3. Before the onset of cell injury, G418 induced reactive oxygen species (ROS) generation, activated oxidative sensitive kinase P38 and caused a shift of connexin 43 (Cx43) from non‐phosphorylated form to hyperphosphorylated form. These changes were largely prevented by antioxidants, suggesting an implication of oxidative stress. Downregulation of Cx43 with inhibitors or siRNA suppressed the expression of thioredoxin‐interacting protein (TXNIP), activated Akt and protected cells against the toxicity of G418. Further analysis revealed that inhibition of TXNIP with siRNA activated Akt and reproduced the protective effect of Cx43‐inhibiting agents, whereas suppression of Akt sensitized cells to the toxicity of G418. Furthermore, interference of TXNIP/Akt also affected puromycin‐ and adriamycin‐induced cell injury. Our study thus characterized TXNIP as a presently unrecognized molecule implicated in the regulatory actions of Cx43 on oxidative drug injury. Targeting Cx43/TXNIP/Akt signalling cascade might be a promising approach to modulate cell response to drugs. 相似文献
93.
Mücella Kirca Petra Kleinbongard Daniel Soetkamp Jacqueline Heger Csaba Csonka Péter Ferdinandy Rainer Schulz 《Journal of cellular and molecular medicine》2015,19(4):815-825
Connexin 43 (Cx43), which is highly expressed in the heart and especially in cardiomyocytes, interferes with the expression of nitric oxide synthase (NOS) isoforms. Conversely, Cx43 gene expression is down‐regulated by nitric oxide derived from the inducible NOS. Thus, a complex interplay between Cx43 and NOS expression appears to exist. As cardiac mitochondria are supposed to contain a NOS, we now investigated the expression of NOS isoforms and the nitric oxide production rate in isolated mitochondria of wild‐type and Cx43‐deficient (Cx43Cre‐ER(T)/fl) mice hearts. Mitochondria were isolated from hearts using differential centrifugation and purified via Percoll gradient ultracentrifugation. Isolated mitochondria were stained with an antibody against the mitochondrial marker protein adenine‐nucleotide‐translocator (ANT) in combination with either a neuronal NOS (nNOS) or an inducible NOS (iNOS) antibody and analysed using confocal laser scanning microscopy. The nitric oxide formation was quantified in purified mitochondria using the oxyhaemoglobin assay. Co‐localization of predominantly nNOS (nNOS: 93 ± 4.1%; iNOS: 24.6 ± 7.5%) with ANT was detected in isolated mitochondria of wild‐type mice. In contrast, iNOS expression was increased in Cx43Cre‐ER(T)/fl mitochondria (iNOS: 90.7 ± 3.2%; nNOS: 53.8 ± 17.5%). The mitochondrial nitric oxide formation was reduced in Cx43Cre‐ER(T)/fl mitochondria (0.14 ± 0.02 nmol/min./mg protein) in comparison to wild‐type mitochondria (0.24 ± 0.02 nmol/min./mg). These are the first data demonstrating, that a reduced mitochondrial Cx43 content is associated with a switch of the mitochondrial NOS isoform and the respective mitochondrial rate of nitric oxide formation. 相似文献
94.
Dysregulation of cytokine expression causes inflammatory diseases or chronic
infection conditions. We have identified that Tat-activating regulatory
DNA-binding protein-43 (TDP-43) is involved in cytokine RNA processing in order
to promote an optimal immune response. The interaction of TDP-43 with
spliceosomal components from the Cajal body leads to the formation of a novel
sub-nuclear body called the Interleukin (IL)-6 and IL-10 Splicing Activating
Compartment (InSAC). TDP-43 binds to the IL-6 and IL-10 RNAs in a
sequence-dependent manner. In cell-based studies, we observed that
lipopoly-saccharide (LPS) stimulation induces the formation of the InSAC through
TDP-43 ubiquitination, thereby influencing the processing and expression levels
of IL-6 RNA. Moreover, TDP-43 knockdown in vivo results in a
decrease in IL-6 production and its RNA splicing and stability. Thus, these
findings demonstrate that the InSAC is linked to the activation and modulation
of the immune response. [BMB Reports 2015; 48(5): 239-240] 相似文献
95.
Takayuki Okamoto Nobuyuki Akita Eiji Kawamoto Tatsuya Hayashi Koji Suzuki Motomu Shimaoka 《Experimental cell research》2014
The gap junction proteins connexin32 (Cx32), Cx37, Cx40, and Cx43 are expressed in endothelial cells, and regulate vascular functions involving inflammation, vasculogenesis and vascular remodeling. Aberrant Cxs expression promotes the development of atherosclerosis which is modulated by angiogenesis; however the role played by endothelial Cxs in angiogenesis remains unclear. In this study, we determined the effects of endothelial Cxs, particularly Cx32, on angiogenesis. EA.hy926 cells that had been transfected to overexpress Cx32 significantly increased capillary length and the number on branches compared to Cx-transfectant cells over-expressing Cx37, Cx40, and Cx43 or mock-treated cells. Treatment via intracellular transfer of anti-Cx32 antibody suppressed tube formation of human umbilical vein endothelial cells (HUVECs) compared to controls. In vitro wound healing assays revealed that Cx32-transfectant cells significantly increased the repaired area while anti-Cx32 antibody-treated HUVECs reduced it. Ex vivo aorta ring assays and in vivo matrigel plaque assays showed that Cx32-deficient mice impaired both vascular sprouting from the aorta and cell migration into the implanted matrigel. Therefore endothelial Cx32 facilitates tube formation, wound healing, vascular sprouting, and cell migration. Our results suggest that endothelial Cx32 positively regulates angiogenesis by enhancing endothelial cell tube formation and cell migration. 相似文献
96.
Xi Xie Cheng Chen Kaipeng Huang Shaogui Wang Jie Hao Junying Huang Heqing Huang 《Experimental cell research》2014
RhoA/Rho kinase (ROCK) signaling has been suggested to be involved in diabetic nephropathy (DN) pathogenesis. Altered expression of connexin43 (Cx43) has been found in kidneys of diabetic animals. Both of them have been found to regulate nuclear factor kappa-B (NF-κB) activation in high glucose-treated glomerular mesangial cells (GMCs). The aim of this study was to investigate the relationship between RhoA/ROCK signaling and Cx43 in the DN pathogenesis. We found that upregulation of Cx43 expression inhibited NF-κB p65 nuclear translocation induced by RhoA/ROCK signaling in GMCs. Inhibition of RhoA/ROCK signaling attenuated the high glucose-induced decrease in Cx43. F-actin accumulation and an enhanced interaction between zonula occludens-1 (ZO-1) and Cx43 were observed in high glucose-treated GMCs. ZO-1 depletion or disruption of F-actin formation also inhibited the reduction in Cx43 protein levels induced by high glucose. In conclusion, activated RhoA/ROCK signaling induces Cx43 degradation in GMCs cultured in high glucose, depending on F-actin regulation. Increased F-actin induced by RhoA/ROCK signaling promotes the association between ZO-1 and Cx43, which possibly triggered Cx43 endocytosis, a mechanism of NF-κB activation in high glucose-treated GMCs. 相似文献
97.
《FEBS letters》2014,588(8):1322-1330
This review summarizes data in support of the notion that the cardiac intercalated disc is the host of a protein interacting network, called “the connexome”, where molecules classically defined as belonging to one particular structure (e.g., desmosomes, gap junctions, sodium channel complex) actually interact with others, and together, control excitability, electrical coupling and intercellular adhesion in the heart. The concept of the connexome is then translated into the understanding of the mechanisms leading to two inherited arrhythmia diseases: arrhythmogenic cardiomyopathy, and Brugada syndrome. The cross-over points in these two diseases are addressed to then suggest that, though separate identifiable clinical entities, they represent “bookends” of a spectrum of manifestations that vary depending on the effect that a particular mutation has on the connexome as a whole. 相似文献
98.
Jun Zou Xiao-Yang Yue Sheng-Chao Zheng Guangwei Zhang He Chang Yan-Chun Liao Ye Zhang Mao-Qiang Xue Zhi Qi 《生物化学与生物物理学报:生物膜》2014
It has been shown that cholesterol modulates activity of protein kinase C (PKC), and PKC phosphorylates connexin 43 (Cx43) to regulate its function, respectively. However, it is not known whether cholesterol modulates function of Cx43 through regulating activity of PKC. In the present study, we demonstrated that cholesterol enrichment reduced the dye transfer ability of Cx43 in cultured H9c2 cells. Western blot analysis indicated that cholesterol enrichment enhanced the phosphorylated state of Cx43. Immunofluorescent images showed that cholesterol enrichment made the Cx43 distribution from condensed to diffused manner in the interface between the cells. In cholesterol enriched cells, PKC antagonists partially restored the dye transfer ability among the cells, downregulated the phosphorylation of Cx43 and redistributed Cx43 from the diffused manner to the condensed manner in the cell interface. In addition, reduction of cholesterol level suppressed PKC activity to phosphorylate Cx43 and restored Cx43 function in PKC agonist-treated cells. Furthermore, we demonstrated that cholesterol enrichment upregulated the phosphorylated state of Cx43 at Ser368, while PKC antagonists reversed the effect. Taken together, cholesterol level in the cells plays important roles in regulating Cx43 function through activation of the PKC signaling pathway. 相似文献
99.
There is an urgent need for animal models of autism spectrum disorder (ASD) to understand the underlying pathology and facilitate development and testing of new treatments. The synaptic growth‐associated protein‐43 (GAP43) has recently been identified as an autism candidate gene of interest. Our previous studies show many brain abnormalities in mice lacking one allele for GAP43 [GAP43 (+/?)] that are consistent with the disordered connectivity theory of ASD. Thus, we hypothesized that GAP43 (+/?) mice would show at least some autistic‐like behaviors. We found that GAP43 (+/?) mice, relative to wild‐type (+/+) littermates, displayed resistance to change, consistent with one of the diagnostic criteria for ASD. GAP43 (+/?) mice also displayed stress‐induced behavioral withdrawal and anxiety, as seen in many autistic individuals. In addition, both GAP43 (+/?) mice and (+/+) littermates showed low social approach and lack of preference for social novelty, consistent with another diagnostic criterion for ASD. This low sociability is likely because of the mixed C57BL/6J 129S3/SvImJ background. We conclude that GAP43 deficiency leads to the development of a subset of autistic‐like behaviors. As these behaviors occur in a mouse that displays disordered connectivity, we propose that future anatomical and functional studies in this mouse may help uncover underlying mechanisms for these specific behaviors. Strain‐specific low sociability may be advantageous in these studies, creating a more autistic‐like environment for study of the GAP43‐mediated deficits of resistance to change and vulnerability to stress. 相似文献
100.
Satoko Ito Hitoki Hasegawa Michinari Hamaguchi 《Biochemical and biophysical research communications》2010,400(2):230-235
Gap junctional communication, which is mediated by the connexin protein family, is essential for the maintenance of normal tissue function and homeostasis. Loss of intercellular communication results in a failure to coordinately regulate cellular functions, and it can facilitate tumorigenesis. Expression of oncogenes and stimulation with cytokines has been shown to suppress intercellular communication; however, the exact mechanism by which intercellular communication is disrupted by these factors remains uncertain. In this report, we show that Akt is essential for the disruption of gap junctional communication in v-Src-transformed cells. In addition, inhibition of Akt restores gap junctional communication after it is suppressed by TNF-α signaling. Furthermore, we demonstrate that the expression of a constitutively active form of Akt1, but not of Akt2 or Akt3, is sufficient to suppress gap junctional communication. Our results clearly define Akt1 as one of the critical regulators of gap junctional communication. 相似文献