全文获取类型
收费全文 | 335篇 |
免费 | 55篇 |
专业分类
390篇 |
出版年
2016年 | 7篇 |
2015年 | 5篇 |
2014年 | 7篇 |
2013年 | 12篇 |
2012年 | 8篇 |
2011年 | 6篇 |
2010年 | 12篇 |
2009年 | 9篇 |
2008年 | 4篇 |
2007年 | 9篇 |
2006年 | 11篇 |
2005年 | 12篇 |
2004年 | 9篇 |
2003年 | 2篇 |
2002年 | 9篇 |
2001年 | 10篇 |
2000年 | 7篇 |
1999年 | 12篇 |
1998年 | 10篇 |
1997年 | 5篇 |
1996年 | 2篇 |
1995年 | 8篇 |
1994年 | 10篇 |
1993年 | 3篇 |
1992年 | 6篇 |
1991年 | 8篇 |
1990年 | 10篇 |
1989年 | 9篇 |
1988年 | 8篇 |
1987年 | 7篇 |
1986年 | 8篇 |
1985年 | 7篇 |
1984年 | 7篇 |
1983年 | 17篇 |
1982年 | 9篇 |
1981年 | 6篇 |
1980年 | 5篇 |
1979年 | 7篇 |
1978年 | 13篇 |
1977年 | 7篇 |
1976年 | 5篇 |
1975年 | 5篇 |
1974年 | 6篇 |
1973年 | 6篇 |
1972年 | 5篇 |
1971年 | 9篇 |
1969年 | 11篇 |
1968年 | 2篇 |
1966年 | 4篇 |
1965年 | 3篇 |
排序方式: 共有390条查询结果,搜索用时 0 毫秒
1.
Conversion of ethanolamine, monomethylethanolamine and dimethylethanolamine to choline-containing compounds by neurons in culture and by the rat brain. 总被引:1,自引:0,他引:1 下载免费PDF全文
C Andriamampandry L Freysz J N Kanfer H Dreyfus R Massarelli 《The Biochemical journal》1989,264(2):555-562
The incubation of neurons from chick embryos in primary culture with [3H]ethanolamine revealed the conversion of this base into monomethyl, dimethyl and choline derivatives, including the corresponding free bases. Labelling with [methyl-3H]monomethylethanolamine and [methyl-3H]dimethylethanolamine supported the conclusion that in chick neuron cultures, phosphoethanolamine appears to be the preferential substrate for methylation, rather than ethanolamine or phosphatidylethanolamine. The methylation of the latter two compounds, in particular that of phosphatidylethanolamine, was seemingly stopped at the level of their monomethyl derivatives. Fetal rat neurons in primary culture incubated with [3H]ethanolamine showed similar results to those observed with chick neurones. However, phosphoethanolamine and phosphatidylethanolamine and, to a lesser extent, free ethanolamine, appeared to be possible substrates for methylation reactions. The methylation of water-soluble ethanolamine compounds de novo was further confirmed by experiments performed in vivo by intraventricular injection of [3H]ethanolamine. Phosphocholine and the monomethyl and dimethyl derivatives of ethanolamine were detected in the brain 15 min after injection. 相似文献
2.
Viviane Hechler Marcel Mersel Henri Dreyfus Michel Maitre 《Molecular and cellular biochemistry》1990,93(1):87-94
Summary -Hydroxybutyric acid (GHB) is a natural compound of mammalian brain synthesized from GABA. The characteristics of its synthesis, transport, release, distribution and turnover, in addition to the presence of a high affinity binding site for this substance in brain are in favor of a modulator role for GHB. The effects of hydrolytic enzymes on the specific binding capacity of GHB have been studied in the present work. Phospholipases A2 and C, neuraminidase and Pronase markedly decrease GHB binding to crude synaptosomal membranes from rat brain. This effect is time and enzyme concentration dependent. Trypsin, under the conditions employed, is less active. The inhibitory effects of phospholipases is correlated with phospholipid hydrolysis. Lysophospholipids, in the absence of bovine fatty acid free serum albumin partially inhibit GHB binding. The action of neuraminidase has been followed by sialic acid release and modifications of the ganglioside profile. The effects of phospholipase C and of neuraminidase are completely different to those on GABA binding sites. These results represent further data concerning the molecular existence of specific GHB binding sites on rat brain membranes.Abbreviations GHB
-hydroxybutyrate
- LPC
L--lysophosphatidylcholine
- LPE
Lysophosphatidylethanolamine
- PC
Phosphatidylcholine
- PE
Phosphatidylethanolamine
- BSA
Bovine Serum Albumin 相似文献
3.
The build-up of the thrombospondin extracellular matrix. An apparent dependence on synthesis and on preformed fibrillar matrix 总被引:3,自引:0,他引:3
Thrombospondin (TSP) is a multifunctional protein synthesized by several cell types in culture, among them endothelial cells, and incorporated into the extracellular matrix (ECM) of these cells. In vitro it has been detected in most interstitial spaces, and its presence has been suggested to be developmentally controlled. With the aim of elucidating the role of TSP in the extracellular matrix, we studied the build-up of this protein in the matrix as a function of cell type density and age in culture. The development of the TSP matrix was compared to that of fibronectin (FN) and of von Willebrand Factor (VWF) in the same cultures using our monoclonal anti-TSP antibody B7-3 and monospecific anti-FN or anti-VWF antibodies. In cultures of bovine aortic endothelial cells (BAEC) we observed that both the pattern and distribution of TSP in the matrix changed with cell density and time in culture; it started as a completely amorphous dense layer of protein when the cells were sparse and changed to well organized fibrils when the cells had been confluent for a while. The first appearance of the fibrillar arrays of TSP coincides perfectly with that of the FN fibers; extracellular VWF also was first detected at this point. From this time in culture, there was an increasing coincidence of the TSP with the FN and the VWF matrices suggesting the formation of a complex multicomponent structure of the fibrillar network.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
4.
Patrick Dreyfus Dina Zevin-Sonkin Shlomo Seidman Catherine Prody Rivka Zisling Haim Zakut Hermona Soreq 《Journal of neurochemistry》1988,51(6):1858-1867
To study the polymorphism of human cholinesterases (ChEs) at the levels of primary sequence and three-dimensional structure, a fragment of human butyrylcholinesterase (BuChE) cDNA was subcloned into the pEX bacterial expression vector and its polypeptide product analyzed. Immunoblot analysis revealed that the clone-produced BuChE peptides interact specifically with antibodies against human and Torpedo acetylcholinesterase (AChE). Rabbit polyclonal antibodies prepared against the purified clone-produced BuChE polypeptides interacted in immunoblots with denatured serum BuChE as well as with purified and denatured erythrocyte AChE. In contrast, native BuChE tetramers from human serum, but not AChE dimers from erythrocytes, interacted with these antibodies in solution to produce antibody-enzyme complexes that could be precipitated by second antibodies and that sedimented faster than the native enzyme in sucrose gradient centrifugation. Furthermore, both AChE and BuChE dimers from muscle extracts, but not BuChE tetramers from muscle, interacted with these antibodies. To reveal further whether the anti-cloned BuChE antibodies would interact in situ with ChEs in the neuromuscular junction, bundles of muscle fibers were microscopically dissected from the region in fetal human diaphragm that is innervated by the phrenic nerve. Muscle fibers incubated with the antibodies and with 125I-Protein A were subjected to emulsion autoradiography, followed by cytochemical ChE staining. The anti-cloned BuChE antibodies, as well as anti-Torpedo AChE antibodies, created patches of silver grains in the muscle endplate region stained for ChE, under conditions where control sera did not. These findings demonstrate that the various forms of human AChE and BuChE in blood and in neuromuscular junctions share sequence homologies, but also display structural differences between distinct molecular forms within particular tissues, as well as between similarly sedimenting molecular forms from different tissues. 相似文献
5.
6.
Primary neurons in culture from chick embryo cerebral hemispheres were treated with a mixture of gangliosides added to the growth medium (final concentration: 10–5M and 10–8M) from the 3rd to the 6th day in vitro. Under these conditions methylation processes measured with [3H] and [35S] methionine and [3H]ethanolamine as precursors showed an increased methylation of [3H]ethanolamine containing phospholipids, a correspondent increased conversion of these compounds to [3H]choline containing phospholipids, and a general increased methylation of trichloroacetic acid precipitable macromolecules containing labeled methionine. A small increase in protein synthesis was observed after incubation of neurons with [3H]- and [35S]methionine. This was confirmed after electrophoretic separation of a protein extract with increased3H-and35S-labeling in protein bands with moecular weights between 50 and 60 KDaltons. A protein band of about 55 KDaltons appeared to be preferentially labelled when [3H] methionine was the precursor. The treatment with gangliosides increased the incorporation of [methyl-3H] label after incubation of neurons with [3H] methionine, into total DNA and decreased that of total RNA. The treatment of neurons in culture with exogenous gangliosides hence affects differently methylation processes, a finding which may confirm the involvement of gangliosides on the intracellular mediation of neuronal information mechanisms. 相似文献
7.
8.
Molecular cloning of cDNA for rat L-type pyruvate kinase and aldolase B 总被引:13,自引:0,他引:13
M P Simon C Besmond D Cottreau A Weber P Chaumet-Riffaud J C Dreyfus J S Trépat J Marie A Kahn 《The Journal of biological chemistry》1983,258(23):14576-14584
Two double-stranded cDNA recombinant pBR322 plasmid libraries were constructed starting from high carbohydrate diet rat liver poly(A)+ mRNA, either fractionated by denaturing sucrose gradient centrifugation for the cloning of L-type pyruvate kinase cDNA, or nonfractionated for aldolase B. Both libraries were screened with single-stranded cDNA probes reverse transcribed from fasted or high carbohydrate diet rat liver mRNAs. mRNAs from fasted animals were also fractionated by sucrose gradient centrifugation and mRNAs from the fed animals were, in addition, further purified by high performance liquid gel filtration chromatography. Those clones hybridizing with the "positive" probe (from animals fed the high carbohydrate diet) and not with the "negative" one (from fasted animals) were preselected and their plasmid DNA was purified and analyzed by positive hybridization-selection. Thirty of 4500 bacteria colonies transformed by recombinant plasmids were preselected by differential screening for pyruvate kinase, and 8 of 864 colonies for aldolase B. Twenty-two recombinant plasmids for pyruvate kinase and two for aldolase B were shown to contain specific cDNA inserts by positive hybridization-selection. Plasmids DNAs of some pyruvate kinase and aldolase B clones (whose inserts ranged from 700 to 1050 bases in length) were labeled by nick translation and used as probes for Northern blot hybridization. The pyruvate kinase cDNA probes recognized mainly a 3400-base RNA species which was detected in high carbohydrate diet rat liver, but not in fasted rat liver and in tissues which do not synthesize L-type pyruvate kinase. In addition, some pyruvate kinase probes hybridized with minor RNA species of about 2000 bases in length, only observed after carbohydrate diet. For aldolase B, the recombinant plasmid DNA hybridized with a single RNA species of 1750 bases. This RNA, detected in kidney, small intestine and liver, was induced by a high carbohydrate diet and increased with liver development. The rat probe cross-hybridized with human aldolase B messenger RNA. 相似文献
9.
Development of catecholaminergic phenotypic characters in the mouse locus coeruleus in vivo and in culture 总被引:1,自引:0,他引:1
While abundant studies have begun to elucidate ontogeny of the peripheral nervous system, molecular mechanisms underlying brain development remain obscure. To approach this problem, we initiated parallel in vivo and in vitro studies of the mouse locus coeruleus (l.c.), a brainstem noradrenergic nucleus. The catecholaminergic enzymes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) were used to monitor phenotype expression and development. TH catalytic activity and immunocytochemical reactivity were initially detectable on gestational Day 13 (E-13) in vivo, and adult levels of activity were approximately by the third postnatal week. Immunotitration studies indicated that the developmental increase was due to accumulation of enzyme molecules and not enzyme activation. The in vivo developmental profile of DBH approximated that of TH. To begin defining regulatory mechanisms, explants of embryonic brainstem were placed in culture. Explantation on E-12, prior to expression of TH or DBH, resulted in the de novo appearance of these phenotypic characters after 4 days. Explantation on E-18, after the enzymes are already expressed, was followed by a striking sixfold rise in TH activity. Immunotitration studies revealed that the increase in TH activity in E-18 cultures was attributable to increased molecule number, reproducing the in vivo results. Moreover, the E-18 explants, cultured for 3 weeks, attained higher plateau levels of TH activity than E-12 cultures, and this differences was due to increased molecule number. Morphometric analysis indicated that 3-week E-12 cultures actually had more l.c. cells than E-18 cultures, indicating that differences in TH were not due to increased cells in the E-18 l.c. Finally, systemic study revealed that the development of TH activity in culture increased progressively from E-11 to E-12 to E-13, suggesting that critical regulatory events occur at this time. Our studies suggest that the l.c. is an excellent model for the study of brain development in vivo and in vitro. Initial phenotypic expression and dramatic development occur in culture in the absence of normal targets, normal afferent innervation and, presumably, normal humoural milieu. 相似文献
10.