全文获取类型
收费全文 | 178篇 |
免费 | 16篇 |
出版年
2022年 | 3篇 |
2021年 | 4篇 |
2018年 | 3篇 |
2017年 | 2篇 |
2016年 | 10篇 |
2015年 | 4篇 |
2014年 | 4篇 |
2013年 | 10篇 |
2012年 | 7篇 |
2011年 | 9篇 |
2010年 | 9篇 |
2009年 | 5篇 |
2008年 | 4篇 |
2007年 | 3篇 |
2006年 | 3篇 |
2005年 | 8篇 |
2004年 | 5篇 |
2003年 | 8篇 |
2002年 | 5篇 |
2001年 | 9篇 |
2000年 | 5篇 |
1999年 | 4篇 |
1998年 | 3篇 |
1997年 | 4篇 |
1995年 | 3篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1987年 | 2篇 |
1986年 | 4篇 |
1983年 | 4篇 |
1981年 | 5篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1967年 | 6篇 |
1966年 | 1篇 |
1964年 | 2篇 |
1963年 | 1篇 |
1961年 | 1篇 |
1959年 | 1篇 |
1957年 | 1篇 |
1956年 | 2篇 |
1952年 | 1篇 |
1950年 | 1篇 |
1943年 | 1篇 |
排序方式: 共有194条查询结果,搜索用时 15 毫秒
51.
52.
Daikoku T Matsumoto H Gupta RA Das SK Gassmann M DuBois RN Dey SK 《The Journal of biological chemistry》2003,278(9):7683-7691
Increased uterine vascular permeability and angiogenesis are hallmarks of implantation and placentation. These events are profoundly influenced by vascular endothelial growth factor (VEGF). We previously showed that VEGF isoforms and VEGF receptors are expressed in the uterus, suggesting the role of VEGF in uterine vascular permeability and angiogenesis required for implantation and decidualization. We have recently shown that estrogen promotes uterine vascular permeability but inhibits angiogenesis, whereas progesterone stimulates angiogenesis with little effect on vascular permeability. However, the mechanism of differential steroid hormonal regulation of uterine angiogenesis remains unresolved. Oxygen homeostasis is essential for cell survival and is primarily mediated by hypoxia-inducible factors (HIFs). These factors are intimately associated with vascular events and induce VEGF expression by binding to the hypoxia response element in the VEGF promoter. HIFalpha isoforms function by forming heterodimers with the aryl hydrocarbon nuclear translocator (ARNT) (HIF-beta) family members. There is very limited information on the relationship among HIFs, ARNTs, and VEGF in the uterus during early pregnancy, although the role of HIFs in regulating VEGF and angiogenesis in cancers is well documented. Using molecular and physiological approaches, we here show that uterine expression of HIFs and ARNTs does not correlate with VEGF expression during the preimplantation period (days 1-4) in mice. In contrast, their expression follows the localization of uterine VEGF expression with increasing angiogenesis during the postimplantation period (days 5-8). This disparate pattern of uterine HIFs, ARNTs, and VEGF expression on days 1-4 of pregnancy suggests HIFs have multiple roles in addition to the regulation of angiogenesis during the peri-implantation period. Using pharmacological, molecular, and genetic approaches, we also observed that although progesterone primarily up-regulates uterine HIF-1alpha expression, estrogen transiently stimulates that of HIF-2alpha. 相似文献
53.
Croft KE Dalby AB Hogan DJ Orr KE Hewitt EA Africa RJ DuBois ML Prescott DM 《Journal of molecular evolution》2003,56(3):341-350
Abstract
The nucleotide sequences of 16 newly reported and 8 previously reported actin-encoding macronuclear DNA molecules in spirotrichs
have been compared. As described for the eight previously reported molecules, the first 50 bases (noncoding) inside the telomere
at both 5′ strands in additional actin molecules are purine-rich. This anomalous base composition might serve as a signal
to identify macronuclear molecules in micronuclear DNA during development. The 50-base segment upstream of the ATG in the
5′ leaders of the actin molecules contains extensive, conserved sequence motifs that are possibly promoter elements. The 3′
noncoding trailers contain virtually no conserved sequence motifs. With one exception, the 3′ trailers contain a second stop
codon (TGA) 36 bases on average downstream of the primary stop codon. Excluding Moneuplotes crassus, amino acid identities in actin I range from 78 to 100%, with variations distributed nonrandomly along the sequence. Phylogenetic
trees based on the actin nucleotide sequences of 22 spirotrichs define the evolutionary relationships of their actin-encoding
molecules. The actin phylogeny, while well supported by posterior probabilities, does not always coincide with the phylogeny
defined in rDNA analyses or classical taxonomic classifications. 相似文献
54.
55.
Simpson LL Maksymowych AB Kouguchi H Dubois G Bora RS Joshi S 《The protein journal》2005,24(3):155-165
Botulinum toxin type A has a long duration of action, and thus it can block transmitter release for several weeks to several months. However, little is known about the precise mechanism that accounts for termination of toxin action. Therefore, experiments were done to gauge the effects of aminopeptidases and carboxypeptidases on the structure and function of the toxin. Exoproteases were added to the holotoxin, the native light chain, and a recombinant light chain. Treated toxin and light chain were examined for their effects on neuromuscular transmission and on isolated substrate. The data showed that aminopeptidase attack did not alter the N-terminus of the toxin/light chain, nor did it produce losses in biological activity. Carboxypeptidase attack did alter the C-terminus of the light chain, but not sufficiently to alter biological activity. The data suggest that the tertiary structure of the light chain confers upon the molecule substantial resistance to exoproteases. 相似文献
56.
Sheng H Shao J Dixon DA Williams CS Prescott SM DuBois RN Beauchamp RD 《The Journal of biological chemistry》2000,275(9):6628-6635
Oncogenic ras induces the expression of cyclooxygenase-2 (COX-2) in a variety of cells. Here we investigated the role of transforming growth factor-beta (TGF-beta) in the Ras-mediated induction of COX-2 in intestinal epithelial cells (RIE-1). RIE-1 cells were transfected with an inducible Ha-Ras(Val12) cDNA and are referred as RIE-iRas cells. the addition of 5 mM isopropyl-1-thio-beta-D-galactopyranoside (IPTG) induced the expression of Ha-Ras(Val12), closely followed by an increase in the expression of COX-2. Neutralizing anti-TGF-beta antibody partially blocked the Ras-induced increase in COX-2. Combined treatment with IPTG and TGF-beta1 resulted in a 20-50-fold increase in the levels of COX-2 mRNA. The t1/2 of COX-2 mRNA was increased from 13 to 24 min by Ha-Ras induction alone. The addition of TGF-beta1 further stabilized the COX-2 mRNA (t1/2 > 50 min). Stable transfection of a luciferase reporter construct containing the COX-2 3'-untranslated region (3'-UTR) revealed that TGF-beta1 treatment and Ras induction each stabilized the COX-2 3'-UTR. Combined treatment with IPTG and TGF-beta1 synergistically increased the luciferase activity. Furthermore, a conserved AU-rich region located in the proximal COX-2 3'-UTR is required for maximal stabilization of COX-2 3'-UTR by Ras or TGF-beta1 and is necessary for the synergistic stabilization of COX-2 3'-UTR by oncogenic Ras and TGF-beta1. 相似文献
57.
Background
Adaptive evolution appears to be a common feature of reproductive proteins across a very wide range of organisms. A promising way of addressing the evolutionary forces responsible for this general phenomenon is to test for adaptive evolution in the same gene but among groups of species, which differ in their reproductive biology. One can then test evolutionary hypotheses by asking whether the variation in adaptive evolution is consistent with the variation in reproductive biology. We have attempted to apply this approach to the study of a female reproductive protein, zona pellucida C (ZPC), which has been previously shown by the use of likelihood ratio tests (LRTs) to be under positive selection in mammals. 相似文献58.
Peters MA Jarvik GP Janer M Chakrabarti L Kolb S Goode EL Gibbs M DuBois CC Schuster EF Hood L Ostrander EA Stanford JL 《Human heredity》2001,51(1-2):107-113
OBJECTIVES: A recent linkage analysis of 360 families at high risk for prostate cancer identified the q27-28 region on chromosome X as the potential location of a gene involved in prostate cancer susceptibility. Here we report on linkage analysis at this putative HPCX locus in an independent set of 186 prostate cancer families participating in the Prostate Cancer Genetic Research Study (PROGRESS). METHODS: DNA samples from these families were genotyped at 8 polymorphic markers spanning 14.3 cM of the HPCX region. RESULTS: Two-point parametric analysis of the total data set resulted in positive lod scores at only two markers, DXS984 and DXS1193, with scores of 0.628 at a recombination fraction (theta) of 0.36 and 0.012 at theta = 0.48, respectively. The stratification of pedigrees according to the assumed mode of transmission increased the evidence of linkage at DXS984 in 81 families with no evidence of male-to-male transmission (lod = 1.062 at theta = 0.28). CONCLUSIONS: Although this analysis did not show statistically significant evidence for the linkage of prostate cancer susceptibility to Xq27-28, the results are consistent with a small percentage of families being linked to this region. The analysis further highlights difficulties in replicating linkage results in an etiologically heterogeneous, complexly inherited disease. 相似文献
59.
Gupta RA Polk DB Krishna U Israel DA Yan F DuBois RN Peek RM 《The Journal of biological chemistry》2001,276(33):31059-31066
Helicobacter pylori colonization leads to epithelial cell hyperproliferation within inflamed mucosa, but levels of apoptosis vary, suggesting that imbalances between rates of cell production and loss may contribute to differences in gastric cancer risk among infected populations. Peroxisome proliferator-activated receptor gamma (PPARgamma) regulates inflammatory and growth responses of intestinal epithelial cells. We determined whether activation of PPARgamma modified H. pylori-induced apoptosis in gastric epithelial cells. PPARgamma was expressed and functionally active in gastric epithelial cell lines sensitive to H. pylori-induced apoptosis. PPARgamma ligands 15d-PGJ(2) and BRL-49653 significantly attenuated H. pylomicronri-induced apoptosis, effects that could be reversed by co-treatment with a specific PPARgamma antagonist. Cyclopentanone prostaglandins that do not bind and activate PPARgamma had no effects on H. pylori-induced apoptosis. The ability of H. pylori to activate nuclear factor (NF)-kappaB and increase levels of the NF-kappaB target IL-8 was blocked by co-treatment with PPARgamma agonists, and direct inhibition of NF-kappaB also abolished H. pylori-stimulated apoptosis. These results suggest that activation of the PPARgamma pathway attenuates the ability of H. pylori to induce NF-kappaB-mediated apoptosis in gastric epithelial cells. Because PPARgamma regulates a multitude of host responses, activation of this receptor may contribute to varying levels of cellular turnover as well as the diverse pathologic outcomes associated with chronic H. pylori colonization. 相似文献
60.
Wang H Guo Y Wang D Kingsley PJ Marnett LJ Das SK DuBois RN Dey SK 《Nature medicine》2004,10(10):1074-1080
Ectopic pregnancy is a major reproductive health issue. Although other underlying causes remain largely unknown, one cause of ectopic pregnancy is embryo retention in the fallopian tube. Here we show that genetic or pharmacologic silencing of cannabinoid receptor CB1 causes retention of a large number of embryos in the mouse oviduct, eventually leading to pregnancy failure. This is reversed by isoproterenol, a beta-adrenergic receptor agonist. Impaired oviductal embryo transport is also observed in wild-type mice treated with methanandamide. Collectively, the results suggest that aberrant cannabinoid signaling impedes coordinated oviductal smooth muscle contraction and relaxation crucial to normal oviductal embryo transport. Colocalization of CB1 and beta2-adrenergic receptors in the oviduct muscularis implies that a basal endocannabinoid tone in collaboration with adrenergic receptors coordinates oviductal motility for normal journey of embryos into the uterus. Besides uncovering a new regulatory mechanism, this study could be clinically relevant to ectopic pregnancy. 相似文献