全文获取类型
收费全文 | 152篇 |
免费 | 23篇 |
出版年
2021年 | 2篇 |
2020年 | 3篇 |
2019年 | 1篇 |
2018年 | 2篇 |
2017年 | 6篇 |
2016年 | 3篇 |
2015年 | 5篇 |
2014年 | 8篇 |
2013年 | 9篇 |
2012年 | 9篇 |
2011年 | 14篇 |
2010年 | 9篇 |
2009年 | 12篇 |
2008年 | 12篇 |
2007年 | 8篇 |
2006年 | 6篇 |
2005年 | 8篇 |
2004年 | 5篇 |
2003年 | 6篇 |
2002年 | 6篇 |
2001年 | 2篇 |
2000年 | 1篇 |
1999年 | 4篇 |
1998年 | 8篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1992年 | 3篇 |
1988年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1975年 | 6篇 |
1971年 | 1篇 |
1954年 | 1篇 |
排序方式: 共有175条查询结果,搜索用时 15 毫秒
1.
Thomas M. Lincoln Stanley L. Keely 《Biochimica et Biophysica Acta (BBA)/General Subjects》1981,676(2):230-244
An assay method based on the ability of high concentrations of Mg2+ to stimulate phosphorylation of histone in the presence of low concentrations of ATP was developed for the measurement of cyclic GMP-dependent protein kinase activity ratios (activity -cyclic GMP/activity + cyclic GMP). In tissues which contain only trace amounts of cyclic GMP-dependent protein kinase, the basal activity ratios were high due to interference from a cyclic nucleotide-independent protein kinase. In order to study the regulation of the cardica cyclic GMP-dependent protein kinase, factors affecting the equilibrium between the active and inactive forms of the enzyme were determined. Since the rate of dissociation of cyclic GMP from its binding site(s) was relatively slow at 0–4°C at pH 7.0, the amount of time required to process tissue samples was the major limiting factor for preserving the equilibrium between active and inactive forms of the enzyme. Dilution of heart tissue extracts at 0–4°C did not significantly alter the activity ratio of the enzyme under conditions of basal or elevated cyclic GMP levels. Experiments using charcoal or exogenous cyclic GMP-dependent protein kinase in the homogenizing medium demonstrated that the release of sequestered cyclic GMP was not responsible for the elevation of the cyclic GMP-dependent protein kinase activity ratios by agents like acetylcholine. Therefore, the assay reflected in part, at least, the retention of kinase-bound cyclic GMP in the tissue extracts. The effects of acetylcholine and sodium nitroprusside on cyclic GMP levels, the cyclic GMP-dependent protein kinase activity ratios, and force of contraction were studied in the perfused rat heart. Both agents produced rapid, dose-dependent increases in cardiac cyclic GMP. Optimal concentrations of acetylcholine produced a 2–3-fold increase in the levels of cyclic GMP and an increase in the cyclic GMP-dependent protein kinase activity ratio. No significant effect of acetylcholine on cyclic nucleotide-independent protein kinase activity was observed. Associated witth the acetylcholine-induced protein kinase, factors affecting the equilibrium between the active and inactive forms of the enzyme were determined. Since the rate of dissociation of cyclic GMP from its binding site(s) was relatively slow at 0–4°C at pH 7.0, the amount of time required to process tissue samples was the major limiting factor for preserving the equilibrium between active and inactive forms of the enzyme. Dilution of heart tissue extracts at 0–4°C did not significantly alter the activity ratio of the enzyme under conditions of basal elevated cyclic GMP levels. Experiments using charcoal or exogenous cyclic GMP-dependent protein kinase in the homogenizing medium demonstrated that the release of sequestered cyclic GMP was not responsible for the elevation of the cyclic GMP-dependent protein kinase activity ratios by agents like acetylcholine. Therefore, the assay reflected in part, at least, the retention of kinase-bound cyclic GMP in the tissue extracts. The effects of acetylcholine and sodium nitroprusside on cyclic GMP levels, the cyclic GMP-dependent protein kinase activity ratios, and force of contraction were studied in the perfused rat heart. Both agents produced rapid, dose-dependent increases in cardiac cyclic GMP. Optimal concentrations of acetylcholine produced a 2–3-fold increase in the levels of cyclic GMP and an increase in the cyclic GMP-dependent protein kinase activity ratio. No significant effect of acetylcholine on cyclic nucleotide-independent protein kinase activity was observed. Associated with the acetylcholine-induced increase in cyclic GMP and the cyclic GMP-dependent protein kinase activity ratio was a reduction in the force of contraction. In contrast, nitroprusside produced little or no increase in the cyclic GMP-dependent protein kinase activity ratio despite increasing the level of cyclic GMP 8–10-fold. Nitroprusside also had no effect on contractile force. In combination, nitroprusside and acetylcholine produced additive effects on cyclic GMP levels, but protein kinase activation and force of contraction were similar to those seen with acetylcholine alone. The results suggest that the cyclic GMP produced by acetylcholine in the rat heart is coupled to activation of the cyclic GMP-dependent protein kinase, while that produced by nitroprusside is not. 相似文献
2.
3.
4.
5.
6.
JF Yuan SJ Zhang O Jafer RA Furlong OE Chausiaux CA Sargent GH Zhang NA Affara 《BMC microbiology》2009,9(1):246
Background
Pseudorabies virus (PRV) is an alphaherpesviruses whose native host is pig. PRV infection mainly causes signs of central nervous system disorder in young pigs, and respiratory system diseases in the adult. 相似文献7.
The components that comprise the extracellular matrix (ECM) are integral to normal tissue homeostasis as well as the development and progression of breast tumors. The secretion, construction, and remodeling of the ECM are each regulated by a complex interplay between tumor cells, fibroblasts and macrophages. Transforming growth factor-β (TGF-β) is an essential molecule in regulating the cellular production of ECM molecules and the adhesive interactions of cells with the ECM. Additionally, hypoxic cell signals, initiated by oxygen deprivation, additional metabolic factors or receptor activation, are associated with ECM formation and the progression of breast cancer. Both TGF-β and hypoxic cell signals are implicated in the functional and morphological changes of cancer-associated-fibroblasts and tumor-associated-macrophages. Moreover, the enhanced recruitment of tumor and stromal cells in response to hypoxia-induced chemokines leads to increased ECM deposition and remodeling, increased blood vessel formation, and enhanced tumor migration. Thus, elucidation of the collaborative networks between tumor and stromal cells in response to the combined signals of TGF-β and hypoxia may yield insight into treatment parameters that target both tumor and stromal cells. 相似文献
8.
9.
Sarah E. Staggs Erin M. Beckman Scott P. Keely Reena Mackwan Michael W. Ware Alan P. Moyer James A. Ferretti Abu Sayed Lihua Xiao Eric N. Villegas 《PloS one》2013,8(6)
Quantitative real-time polymerase chain reaction (qPCR) assays to detect Cryptosporidium oocysts in clinical samples are increasingly being used to diagnose human cryptosporidiosis, but a parallel approach for detecting and identifying Cryptosporidium oocyst contamination in surface water sources has yet to be established for current drinking water quality monitoring practices. It has been proposed that Cryptosporidium qPCR-based assays could be used as viable alternatives to current microscopic-based detection methods to quantify levels of oocysts in drinking water sources; however, data on specificity, analytical sensitivity, and the ability to accurately quantify low levels of oocysts are limited. The purpose of this study was to provide a comprehensive evaluation of TaqMan-based qPCR assays, which were developed for either clinical or environmental investigations, for detecting Cryptosporidium oocyst contamination in water. Ten different qPCR assays, six previously published and four developed in this study were analyzed for specificity and analytical sensitivity. Specificity varied between all ten assays, and in one particular assay, which targeted the Cryptosporidium 18S rRNA gene, successfully detected all Cryptosporidium spp. tested, but also cross-amplified T. gondii, fungi, algae, and dinoflagellates. When evaluating the analytical sensitivity of these qPCR assays, results showed that eight of the assays could reliably detect ten flow-sorted oocysts in reagent water or environmental matrix. This study revealed that while a qPCR-based detection assay can be useful for detecting and differentiating different Cryptosporidium species in environmental samples, it cannot accurately measure low levels of oocysts that are typically found in drinking water sources. 相似文献
10.
Gold salts and phenylbutazone selectively inhibit the synthesis of PGF2α and PGE2 respectively. Lowered production of one prostaglandin species is accompanied by an increased production of the other. Selective inhibition by these drugs was observed in the presence of adrenaline, reduced glutathione and copper sulphate under conditions when most anti-inflammatory compounds inhibited PGE2 and PGF2α syntheses equally. It is postulated that selective inhibitors may have a different mode of action
and beneficial effects may be related to the endogenous ratio of PGE to PGF required for normal function. 相似文献