全文获取类型
收费全文 | 397篇 |
免费 | 32篇 |
出版年
2023年 | 1篇 |
2022年 | 7篇 |
2021年 | 8篇 |
2020年 | 2篇 |
2019年 | 5篇 |
2018年 | 4篇 |
2017年 | 4篇 |
2016年 | 19篇 |
2015年 | 21篇 |
2014年 | 18篇 |
2013年 | 27篇 |
2012年 | 42篇 |
2011年 | 39篇 |
2010年 | 21篇 |
2009年 | 21篇 |
2008年 | 43篇 |
2007年 | 34篇 |
2006年 | 21篇 |
2005年 | 28篇 |
2004年 | 18篇 |
2003年 | 12篇 |
2002年 | 14篇 |
2001年 | 3篇 |
2000年 | 4篇 |
1999年 | 3篇 |
1998年 | 6篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1994年 | 1篇 |
1986年 | 1篇 |
排序方式: 共有429条查询结果,搜索用时 31 毫秒
71.
Glypican-1 regulates anaphase promoting complex/cyclosome substrates and cell cycle progression in endothelial cells 总被引:1,自引:0,他引:1
Glypican-1 (GPC1), a member of the mammalian glypican family of heparan sulfate proteoglycans, is highly expressed in glioma blood vessel endothelial cells (ECs). In this study, we investigated the role of GPC1 in EC replication by manipulating GPC1 expression in cultured mouse brain ECs. Moderate GPC1 overexpression stimulates EC growth, but proliferation is significantly suppressed when GPC1 expression is either knocked down or the molecule is highly overexpressed. Flow cytometric and biochemical analyses show that high or low expression of GPC1 causes cell cycle arrest at mitosis or the G2 phase of the cell cycle, accompanied by endoreduplication and consequently polyploidization. We further show that GPC1 inhibits the anaphase-promoting complex/cyclosome (APC/C)-mediated degradation of mitotic cyclins and securin. High levels of GPC1 induce metaphase arrest and centrosome overproduction, alterations that are mimicked by overexpression of cyclin B1 and cyclin A, respectively. These observations suggest that GPC1 regulates EC cell cycle progression at least partially by modulating APC/C-mediated degradation of mitotic cyclins and securin. 相似文献
72.
Will K Reeves Kristy O Murray Tamra E Meyer Lara M Bull Rhia F Pascua Kelly C Holmes Amanda D Loftis 《Journal of vector ecology》2008,33(1):205-207
We tested sera from 176 homeless people in Houston for antibodies against typhus group rickettsiae (TGR). Sera from 19 homeless people were reactive to TGR antigens by ELISA and IFA. Two people had antibodies against Rickettsia prowazekii (epidemic typhus) and the remaining 17 had antibodies against Rickettsia typhi (murine typhus). 相似文献
73.
Summary: We developed an interactive gene ontology (GO) browsernamed GOTreePlus that superimposes annotation information overGO structures. It can facilitate the identification of importantGO terms through interactive visualization of them in the GOstructure. The interactive pie chart summarizing an annotationdistribution for a selected GO term provides users with a succinctcontext-sensitive overview of their experimental results. Wetested our GOTreePlus using a proteome profiling dataset obtainedon differentiation of retinal pigment epithelial cells where399 proteins were quantified. Availability: http://bioinformatics.cnmcresearch.org/GOTreePlus/ Contact: jseo{at}cnmcresearch.org
Associate Editor: John Quackenbush 相似文献
74.
Ray C. Bartolo Natalie Harfoot Mike Gill Kristy Demmers Bernie McLeod A. Grant Butt 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2009,179(8):997-1010
The colon of the brushtail possum does not have an electrogenic secretory response. Given the functional significance of electrogenic
Cl− secretion in the intestine of eutherian mammals, we have investigated the secretory response in the small intestine of this
marsupial. In the Ussing chamber cAMP-dependent secretagogues stimulated a sustained increase in ileal short-circuit current
(Isc), whereas Ca2+-dependent secretagogues induced a transient increase. Both the responses were inhibited by mucosal addition of the anion
channel blocker 5-nitro-2-(3-phenylpropylamino) benzoic acid (100 μmol l−1), consistent with an anion secretory response. However, the responses were not inhibited by serosal bumetanide (10 μmol l−1) and were independent of bath Cl−, indicating that the stimulated ileal Isc does not involve electrogenic Cl− secretion driven by the NaK2Cl cotransporter, NKCC1. Consistent with this, there were low levels of NKCC1 expression in the
ileal epithelium. In particular, NKCC1 expression in the ileal crypt cells was comparable to that of the villous cells. This
differs from eutherian mammals where high levels of NKCC1 expression in the ileal crypt cells are associated with their role
in Cl− secretion. The cAMP- and Ca2+-dependent secretory responses were inhibited by the removal of HCO3
− suggesting that these responses were due to electrogenic HCO3
− secretion. We conclude that the ileum of the possum does not secrete Cl− due to low levels of NKCC1 expression. It does however appear to secrete HCO3
−. These results are further significant examples of differences in the transport function of the possum intestinal epithelium
compared with eutherian mammals. 相似文献
75.
Willmarth NE Baillo A Dziubinski ML Wilson K Riese DJ Ethier SP 《Cellular signalling》2009,21(2):212-219
The epidermal growth factor receptor (EGFR) and its ligand amphiregulin (AR) have been shown to be co-over expressed in breast cancer. We have previously shown that an AR/EGFR autocrine loop is required for SUM149 human breast cancer cell proliferation, motility and invasion. We also demonstrated that AR can induce these altered phenotypes when expressed in the normal mammary epithelial cell line MCF10A, or by exposure of these cells to AR in the medium. In the present studies, we demonstrate that SUM149 cells and immortalized human mammary epithelial MCF10A cells that over express AR (MCF10A AR) or are cultured in the presence of exogenous AR, express higher levels of EGFR protein than MCF10A cells cultured in EGF. Pulse-chase analysis showed that EGFR protein remained stable in the presence of AR, yet was degraded in the presence of EGF. Consistent with this observation, tyrosine 1045 on the EGFR, the c-cbl binding site, exhibited less phosphorylation following stimulation with AR than following stimulation with EGF. Ubiquitination of the receptor was also dramatically less following stimulation with AR than following stimulation with EGF. Flow cytometry analysis showed that EGFR remained on the cell surface following stimulation with AR but was rapidly internalized following stimulation with EGF. Immunofluorescence and confocal microscopy confirmed the flow cytometry results. EGFR in MCF10A cells cultured in the presence of EGF exhibited a predominantly intracellular, punctate localization. In stark contrast, SUM149 cells and MCF10A cells growing in the presence of AR expressed EGFR predominantly on the membrane and at cell-cell junctions. We propose that AR alters EGFR internalization and degradation in a way that favors accumulation of EGFR at the cell surface and ultimately leads to changes in EGFR signaling. 相似文献
76.
77.
78.
Tomohiro Nishimura Michinori Kohara Kosuke Izumi Yuri Kasama Yuichi Hirata Ying Huang Masahiro Shuda Chise Mukaidani Takashi Takano Yuko Tokunaga Hideko Nuriya Masaaki Satoh Makoto Saito Chieko Kai Kyoko Tsukiyama-Kohara 《The Journal of biological chemistry》2009,284(52):36442-36452
Persistent infection with hepatitis C virus (HCV) induces tumorigenicity in hepatocytes. To gain insight into the mechanisms underlying this process, we generated monoclonal antibodies on a genome-wide scale against an HCV-expressing human hepatoblastoma-derived cell line, RzM6-LC, showing augmented tumorigenicity. We identified 3β-hydroxysterol Δ24-reductase (DHCR24) from this screen and showed that its expression reflected tumorigenicity. HCV induced the DHCR24 overexpression in human hepatocytes. Ectopic or HCV-induced DHCR24 overexpression resulted in resistance to oxidative stress-induced apoptosis and suppressed p53 activity. DHCR24 overexpression in these cells paralleled the increased interaction between p53 and MDM2 (also known as HDM2), a p53-specific E3 ubiquitin ligase, in the cytoplasm. Persistent DHCR24 overexpression did not alter the phosphorylation status of p53 but resulted in decreased acetylation of p53 at lysine residues 373 and 382 in the nucleus after treatment with hydrogen peroxide. Taken together, these results suggest that DHCR24 is elevated in response to HCV infection and inhibits the p53 stress response by stimulating the accumulation of the MDM2-p53 complex in the cytoplasm and by inhibiting the acetylation of p53 in the nucleus. 相似文献
79.
We tested for disproportional changes in annual and seasonal species richness and biomass among five trophic levels (phytoplankton,
herbivorous, omnivorous, and carnivorous zooplankton, and fish) as well as altered trophic structure and ecosystem function
following the 5-year experimental acidification of Little Rock Lake (Wisconsin, USA) from pH 6.1 to 4.7. Abiotic and biotic
controls of trophic level response during acidification were also identified. Asymmetric reductions of species richness among
trophic levels, separated by life stage and feeding type, were evident and changes in trophic structure were most pronounced
by the end of the acidification period. Relative declines in richness of fish and zooplankton were greater than phytoplankton,
which were generally unaffected, leading to a reduction of upper trophic level diversity. Each of the lower four trophic levels
responded to a distinct combination of abiotic and biotic variables during acidification. pH was identified as a direct driver
of change for only carnivorous zooplankton, while all other trophic levels were affected more by indirect interactions caused
by acidification. Fluctuations in ecosystem function (zooplankton biomass and primary production) were also evident, with
losses at all trophic levels only detected during the last year of acidification. The acidified basin displayed a tendency
for greater variation in biomass for upper trophic levels relative to reference conditions implying greater unpredictability
in ecosystem function. Together, these results suggest that trophic asymmetry may be an important and recurring feature of
ecosystem response to anthropogenic stress. 相似文献
80.