全文获取类型
收费全文 | 199篇 |
免费 | 34篇 |
出版年
2016年 | 3篇 |
2015年 | 6篇 |
2014年 | 3篇 |
2013年 | 6篇 |
2012年 | 4篇 |
2008年 | 3篇 |
2007年 | 5篇 |
2006年 | 4篇 |
2005年 | 10篇 |
2004年 | 5篇 |
2003年 | 6篇 |
2002年 | 8篇 |
2001年 | 10篇 |
2000年 | 6篇 |
1999年 | 12篇 |
1998年 | 2篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 4篇 |
1993年 | 3篇 |
1992年 | 5篇 |
1991年 | 6篇 |
1990年 | 9篇 |
1989年 | 9篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1986年 | 2篇 |
1985年 | 5篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 7篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1977年 | 5篇 |
1976年 | 2篇 |
1975年 | 5篇 |
1974年 | 4篇 |
1973年 | 9篇 |
1972年 | 2篇 |
1971年 | 6篇 |
1970年 | 3篇 |
1969年 | 1篇 |
1968年 | 8篇 |
1967年 | 6篇 |
1966年 | 2篇 |
1965年 | 2篇 |
1956年 | 2篇 |
排序方式: 共有233条查询结果,搜索用时 281 毫秒
101.
102.
CD39 can exist in at least two distinct functional states depending on the presence and intact membrane integration of its two transmembrane helices. In native membranes, the transmembrane helices undergo dynamic rotational motions that are required for enzymatic activity and are regulated by substrate binding. In this study, we show that bilayer mechanical properties regulate conversion between the two enzymatic functional states by modulating transmembrane helix dynamics. Alteration of membrane properties by insertion of cone-shaped or inverse cone-shaped amphiphiles or by cholesterol removal switches CD39 to the same enzymatic state that removal or solubilization of the transmembrane domains does. The same membrane alterations increase the propensity of both transmembrane helices to rotate within the packed structure, resulting in a structure with greater mobility but not an altered primary conformation. Membrane alteration also abolishes the ability of the substrate to stabilize the helices in their primary conformation, indicating a loss of coupling between substrate binding and transmembrane helix dynamics. Removal of either transmembrane helix mimics the effect of membrane alteration on the mobility and substrate sensitivity of the remaining helix, suggesting that the ends of the extracellular domain have intrinsic flexibility. We suggest that a mechanical bilayer property, potentially elasticity, regulates CD39 by altering the balance between the stability and flexibility of its transmembrane helices and, in turn, of its active site. 相似文献
103.
Pinna G Agis-Balboa RC Pibiri F Nelson M Guidotti A Costa E 《Neurochemical research》2008,33(10):1990-2007
The neurosteroid allopregnanolone is a potent positive allosteric modulator of GABA action at GABAA receptors. Allopregnanolone is synthesized in the brain from progesterone by the sequential action of 5α-reductase type I
(5α-RI) and 3α-hydroxysteroid dehydrogenase (3α-HSD). 5α-RI and 3α-HSD are co-expressed in cortical, hippocampal, and olfactory
bulb glutamatergic neurons and in output neurons of the amygdala, thalamus, cerebellum, and striatum. Neither 5α-RI nor 3α-HSD
mRNAs is expressed in glial cells or in cortical or hippocampal GABAergic interneurons. It is likely that allopregnanolone
synthesized in principal output neurons locally modulates GABAA receptor function by reaching GABAA receptor intracellular sites through lateral membrane diffusion.
This review will focus on the behavioral effects of allopregnanolone on mouse models that are related to a sexually dimorphic
regulation of brain allopregnanolone biosynthesis. Animal models of psychiatric disorders, including socially isolated male
mice or mice that receive a long-term treatment with anabolic androgenic steroids (AAS), show abnormal behaviors such as altered
fear responses and aggression. In these animal models, the cortico-limbic mRNA expression of 5α-RI is regulated in a sexually
dimorphic manner. Hence, in selected glutamatergic pyramidal neurons of the cortex, CA3, and basolateral amygdala and in granular
cells of the dentate gyrus, mRNA expression of 5α-RI is decreased, which results in a downregulation of allopregnanolone content.
In contrast, 5α-RI mRNA expression fails to change in the striatum medium spiny neurons and in the reticular thalamic nucleus
neurons, which are GABAergic.
By manipulating allopregnanolone levels in glutamatergic cortico-limbic neurons in opposite directions to improve [using the
potent selective brain steroidogenic stimulant (SBSS) S-norfluoxetine] or induce (using the potent 5α-RI inhibitor SKF 105,111)
behavioral deficits, respectively, we have established the fundamental role of cortico-limbic allopregnanolone levels in the
sexually dimorphic regulation of aggression and fear. By selectively targeting allopregnanolone downregulation in glutamatergic
cortico-limbic neurons, i.e., by improving the response of GABAA receptors to GABA, new therapeutics would offer appropriate and safe management of psychiatric conditions, including impulsive
aggression, irritability, irrational fear, anxiety, posttraumatic stress disorders, and depression.
Special issue article in honor of Dr. Ji-Sheng Han. 相似文献
104.
105.
106.
107.
R Franchi-Gazzola G C Gazzola V Dall'Asta G G Guidotti 《The Journal of biological chemistry》1982,257(16):9582-9587
The transport of L-alanine, L-serine, and L-cysteine has been studied in skin-derived diploid human fibroblasts in culture. Competition analysis, mathematical discrimination by nonlinear regression, and conditions varying the relative contribution of the various mediations have been used to characterize the systems engaged in the inward transport of these amino acids. All the adopted criteria yielded results showing that L-alanine, L-serine, and L-cysteine enter the cell by two Na+-dependent systems, System A and System ASC, and by a Na+-independent route, whose major component has been identified as System L. The apparent affinity of L-alanine, L-serine, and L-cysteine for the putative carrier was higher for System ASC than for System A. The transport Vmax for System A increased in response to cell starvation; after 12 h, its values were similar or higher than those exhibited by System ASC. At amino acid concentrations approaching those present in human plasma, System ASC appeared to be the primary mediation for the inward transport of L-alanine, L-serine, and L-cysteine in human fibroblasts. The contribution of System A was negligible in nonstarved cells and became appreciable under conditions of cell starvation. The Na+-independent System L made no substantial contribution to the uptake of L-alanine and L-serine and accounted for approximately one-fourth of the total uptake of L-cysteine. 相似文献
108.
Angelo F. Borghetti Giuseppe Piedimonte Mariarosaria Tramacere Alberto Severini Paolo Ghiringhelli Guido G. Guidotti 《Journal of cellular physiology》1980,105(1):39-49
The transport of selected neutral and cationic amino acids has been studied in Balb/c 3T3, SV3T3, and SV3T3 revertant cell lines. After properly timed preincubations to control the size of internal amino acid pools, the activity of systems A, ASC, L, and Ly+ has been discriminated by measurements of amino acid uptake (initial entry rate) in the presence and absence of sodium and of transportspecific model substrates. L-Proline, 2-aminoisobutyric acid, and glycine were primarily taken up by system A; L-alanine and L-serine by system ASC; L-phenylalanine by system L; and L-lysine by system Ly+ in SV3T3 cells. L-Proline and L-serine were also preferential substrates of systems A and ASC, respectively, in 3T3 and SV3T3 revertant cells. Transport activity of the Na+-dependent systems A and ASC decreased markedly with the increase of cell density, whereas the activity of the Na+-independent systems L and Ly+remained substantially unchanged. The density-dependent change in activity of system A occurred through a mechanism affecting transport maximum (Vmax) rather than substrate concentration for half-maximal velocity (Km). Transport activity of systems A and ASC was severalfold higher in transformed SV3T3 cells than in 3T3 parental cells at all the culture densities that could be compared. In SV3T3 revertant cells, transport activity by these systems remained substantially similar to that observed in transformed SV3T3 cells. The results presented here add cell density as a regulatory factor of the activity of systems A and ASC, and show that this control mechanism of amino acid transport is maintained in SV40 virus-transformed 3T3 cells that have lost density-dependent inhibition of growth, as well as in SV3T3 revertant cells that have resumed it. 相似文献
109.
Jeffrey D. Rothstein William Garland Gulia Puia Alessandro Guidotti Richard J. Weber Erminio Costa 《Journal of neurochemistry》1992,58(6):2102-2115
Chemicals that are active at the benzodiazepine receptor (endozepines) are naturally present in the CNS. These substances are present in tissue from humans and animals and in plants and fungi. Using selective extraction protocols, HPLC purification, receptor binding displacement studies, and selective anti-benzodiazepine antibodies, we have identified six or seven peaks of endozepines in rat and human brain. All material could competitively displace [3H]flunitrazepam binding to cerebellar benzodiazepine binding sites. Two peaks also competitively displaced Ro 5-4864 binding to the mitochondrial benzodiazepine binding site. Total amounts of brain endozepines were estimated to be present in potentially physiological concentrations, based on their ability to displace [3H]flunitrazepam binding. Although endozepine peaks 1 and 2 had HPLC retention profiles similar to those of nordiazepam and diazepam, respectively, gas chromatography-mass spectrometry as well as high-performance TLC revealed biologically insignificant amounts of diazepam (less than 0.02 pg/g) and nordiazepam (less than 0.02 pg/g) in the purified material. Electrophysiologically, some purified endozepines positively modulated gamma-aminobutyric acid (GABA) action on Cl- conductance, monitored in patch-clamped cultured cortical neurons or in mammalian cells transfected with cDNA encoding various GABAA receptor subunits. These studies demonstrate that mammalian brains contain endozepines that could serve as potent endogenous positive allosteric modulators of GABAA receptors. 相似文献
110.
Insulin regulation of amino acid transport in mesenchymal cells from avian and mammalian tissues. 总被引:1,自引:1,他引:0
下载免费PDF全文
![点击此处可从《The Biochemical journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
G G Guidotti A F Borghetti G C Gazzola M Tramacere V Dall''asta 《The Biochemical journal》1976,160(2):281-286
Insulin regulation of amino acid transport across the cell membrane was studied in a variety of mesenchymal cell directly isolated from avian and mammalian tissues or collected from confluent cultures. Transport activity of the principal systems of mediation in the presence and absence of insulin was evaluated by measuring the uptake of representative amino acids under conditions approaching initial entry rates. Insulin enhanced the transport rate of substrate amino acids from the A system(alpha-aminoisobutyric acid, L-proline, glycine, L-alanine and L-serine) in fibroblasts and osteoblasts from chick-embryo tissues, in mesenchymal cells (fibroblasts and smooth muscle cells) from immature rat uterus, in thymic lymphocytes from young rats and in chick-embryo fibroblasts from confluent secondary cultures. In these tissues, the uptake of amino acid substrates of transport systems L and Ly+ (L-leucine, L-phenylalanine, L-lysine) was not affected by the presence of the hormone. No insulin control of amino acid transport was detected in chick-embryo chondroblasts and rat peritoneal macrophages. These observations identify the occurrence of hormonal regulatory patterns of amino acid transport for different mesenchymal cells types and indicate that these properties emerge early during cell differentiation. 相似文献