全文获取类型
收费全文 | 226篇 |
免费 | 7篇 |
专业分类
233篇 |
出版年
2022年 | 1篇 |
2021年 | 2篇 |
2018年 | 3篇 |
2017年 | 2篇 |
2016年 | 4篇 |
2015年 | 5篇 |
2014年 | 6篇 |
2013年 | 14篇 |
2012年 | 10篇 |
2011年 | 12篇 |
2010年 | 12篇 |
2009年 | 11篇 |
2008年 | 16篇 |
2007年 | 13篇 |
2006年 | 14篇 |
2005年 | 4篇 |
2004年 | 13篇 |
2003年 | 5篇 |
2002年 | 11篇 |
2001年 | 6篇 |
2000年 | 3篇 |
1999年 | 3篇 |
1998年 | 6篇 |
1997年 | 2篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1978年 | 1篇 |
1977年 | 5篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1971年 | 2篇 |
1970年 | 2篇 |
1969年 | 4篇 |
1968年 | 3篇 |
1967年 | 3篇 |
1966年 | 1篇 |
排序方式: 共有233条查询结果,搜索用时 10 毫秒
81.
82.
Idiopathic pulmonary fibrosis (IPF) is the most common and severe type of idiopathic interstitial pneumonias (IIP), and which is currently no method was developed to restore normal structure and function. There are several reports on therapeutic effects of adult stem cell transplantations in animal models of pulmonary fibrosis. However, little is known about how mesenchymal stem cell (MSC) can repair the IPF. In this study, we try to provide the evidence to show that transplanted mesenchymal stem cells directly replace fibrosis with normal lung cells using IPF model mice. As results, transplanted MSC successfully integrated and differentiated into type II lung cell which express surfactant protein. In the other hand, we examine the therapeutic effects of microvesicle treatment, which were released from mesenchymal stem cells. Though the therapeutic effects of MV treatment is less than that of MSC treatment, MV treat-ment meaningfully reduced the symptom of IPF, such as collagen deposition and inflammation. These data suggest that stem cell transplantation may be an effective strategy for the treatment of pulmonary fibrosis via replacement and cytoprotective effect of microvesicle released from MSCs. 相似文献
83.
Hye-Min Park Goo-Young Kim Min-Kyung Nam Geun-Hye Seong Kwang Chul Chung Hyangshuk Rhim 《Biochemical and biophysical research communications》2009,387(3):537-29
The serine protease HtrA2 is important in regulating not only apoptosis but also cellular homeostasis. Recently, several lines of evidence suggest that HtrA2 may be intimately associated with Parkin; however, little is known about the functional relationships between HtrA2 and Parkin. Here we have shown that HtrA2 is co-localized with Parkin in the cytosol through the release of HtrA2 from the mitochondria upon cellular stresses. Moreover, endogenous levels of Parkin were significantly decreased in wild-type (HtrA2+/+) mouse embryonic fibroblasts (MEF) compared with those in HtrA2-knockout (HtrA2−/−) MEF under the same stress conditions. Using cleavage and binding assays, we have demonstrated that HtrA2 specifically binds to and directly cleaves the E3 ubiquitin (Ub) ligase Parkin. Interestingly, the HtrA2-mediated Parkin cleavage irreversibly disrupts Parkin-mediated synphilin-1 ubiquitination and autoubiquitination, indicating that HtrA2 may play a critical role in the Parkin-related pathway involved in the ubiquitin proteasome system. 相似文献
84.
Park HJ Kim SS Seong YM Kim KH Goo HG Yoon EJ Min do S Kang S Rhim H 《The Journal of biological chemistry》2006,281(45):34277-34287
The processing and metabolism of amyloid precursor protein (APP) is a major interest in Alzheimer disease (AD) research, because not only amyloid beta (Abeta) peptide, but also cellular or mitochondrial APP are intimately involved in cellular dysfunction and AD pathogenesis. Here we demonstrate that APP is directly and efficiently cleaved by the HtrA2 serine protease in vitro and in vivo. Using several APP mutants and N-terminal amino acid sequencing, we identified that the HtrA2-mediated APP cleavage product is the C161 fragment encompassing amino acids 535-695 of APP695. The immunofluorescence and subcellular fractionation studies indicate that APP is partly colocalized with HtrA2 in the mitochondria where HtrA2 can cleave APP under normal conditions. The HtrA2-cleaved C161 fragment was detected in the cytosolic fraction; therefore, we postulate that the C161 fragment is released into the cytosol after cleavage of APP by HtrA2. Interestingly, the level of C161 was remarkably decreased in motor neuron degeneration (mnd2) mice in which the serine protease activity of HtrA2 was greatly reduced. These results show that the protease activity of HtrA2 is essential for the production of C161 and that processing of APP into C161 is a natural event occurring under normal physiological conditions. Our study suggests that the direct cleavage of mitochondrial APP by HtrA2 may prevent mitochondrial dysfunction caused by accumulation of APP and that the regulation of HtrA2 protease activity may be a therapeutic target in AD. 相似文献
85.
Bifidobacterium adolescentis Int-57 (INT57), isolated from human feces, secretes an amylase. We have shot-gun cloned, sequence analyzed and expressed
the gene encoding this amylase in B. longum. The sequenced 2477 bp fragment was homologous to other extracellular amylases. The encoded protein was predicted to be composed
of 595 amino acids with a molecular weight of 64 kDa, and was designated AmyB. Highly conserved amylase domains were found
in AmyB. The signal sequence and cleavage site was predicted by sequence analysis. AmyB was subcloned into pBES2, a novel E. coli–Bifidobacterium shuttle vector, to construct pYBamy59. Subsequently, B. longum, with no apparent amylase activity, was transformed with pYBamy59. More than 90% of the amylase activity was detected in
the culture broth. This approach may open the way for the development of more efficient expression and secretion systems for
Bifidobacterium.
Both authors contributed equally
Received 17 June 2005; Revisions requested 13 July 2005 and 26 September 2005; Revisions received 12 September 2005 and 8
November 2005; Accepted 11 November 2005 相似文献
86.
Phenotypic characterization of telomerase-immortalized primary non-malignant and malignant tumor-derived human prostate epithelial cell lines 总被引:5,自引:0,他引:5
Gu Y Li H Miki J Kim KH Furusato B Sesterhenn IA Chu WS McLeod DG Srivastava S Ewing CM Isaacs WB Rhim JS 《Experimental cell research》2006,312(6):831-843
In vitro human prostate cell culture models are critical for clarifying the mechanism of prostate cancer progression and for testing preventive and therapeutic agents. Cell lines ideal for the study of human primary prostate tumors would be those derived from spontaneously immortalized tumor cells; unfortunately, explanted primary prostate cells survive only short-term in culture, and rarely immortalize spontaneously. Therefore, we recently have generated five immortal human prostate epithelial cell cultures derived from both the benign and malignant tissues of prostate cancer patients with telomerase, a gene that prevents cellular senescence. Examination of these cell lines for their morphologies and proliferative capacities, their abilities to grow in low serum, to respond to androgen stimulation, to grow above the agar layer, to form tumors in SCID mice, suggests that they may serve as valid, useful tools for the elucidation of early events in prostate tumorigenesis. Furthermore, the chromosome alterations observed in these immortalized cell lines expressing aspects of the malignant phenotypes imply that these cell lines accurately recapitulate the genetic composition of primary tumors. These novel in vitro models may offer unique models for the study of prostate carcinogenesis and also provide the means for testing both chemopreventive and chemotherapeutic agents. 相似文献
87.
Yoo Lim Kam Hee-Kyung Rhee Hyewhon Rhim Seung Keun Back Heung Sik Na Hea-Young Park Choo 《Bioorganic & medicinal chemistry》2010,18(16):5938-5944
Novel diphenylpiperazine derivatives were synthesized and evaluated for their inhibitory activity against T-type calcium channel by whole-cell patch clamp recordings on HEK293 cells. Among the test compounds, 2 and 3d were effective in decreasing the response to formalin in both the first and second phases and demonstrated antiallodynic effects in a rat model of neuropathic pain. 相似文献
88.
89.
Jungsun Kim John P. Hoffman R. Katherine Alpaugh Andrew D. Rhim Maximilian Reichert Ben Z. Stanger Emma E. Furth Antonia R. Sepulveda Chao-Xing Yuan Kyoung-Jae Won Greg Donahue Jessica Sands Andrew A. Gumbs Kenneth S. Zaret 《Cell reports》2013,3(6):2088-2099
- Download : Download full-size image
90.
The extracellular matrix (ECM) provides an essential structural framework for cell attachment, proliferation, and differentiation,
and undergoes progressive changes during senescence. To investigate changes in protein expression in the extracellular matrix
between young and senescent fibroblasts, we compared proteomic data (LTQ-FT) with cDNA microarray results. The peptide counts
from the proteomics analysis were used to evaluate the level of ECM protein expression by young cells and senescent cells,
and ECM protein expression data were compared with the microarray data. After completing the comparative analysis, we grouped
the genes into four categories. Class I included genes with increased expression levels in both analyses, while class IV contained
genes with reduced expression in both analyses. Class II and Class III contained genes with an inconsistent expression pattern.
Finally, we validated the comparative analysis results by examining the expression level of the specific gene from each category
using Western blot analysis and semiquantitative RT-PCR. Our results demonstrate that comparative analysis can be used to
identify differentially expressed genes. 相似文献