全文获取类型
收费全文 | 233篇 |
免费 | 12篇 |
专业分类
245篇 |
出版年
2023年 | 2篇 |
2022年 | 3篇 |
2021年 | 7篇 |
2020年 | 3篇 |
2019年 | 7篇 |
2018年 | 3篇 |
2017年 | 9篇 |
2016年 | 3篇 |
2015年 | 8篇 |
2014年 | 13篇 |
2013年 | 11篇 |
2012年 | 12篇 |
2011年 | 20篇 |
2010年 | 12篇 |
2009年 | 4篇 |
2008年 | 12篇 |
2007年 | 10篇 |
2006年 | 4篇 |
2005年 | 6篇 |
2004年 | 9篇 |
2003年 | 9篇 |
2002年 | 5篇 |
2001年 | 11篇 |
2000年 | 6篇 |
1999年 | 7篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1992年 | 5篇 |
1991年 | 5篇 |
1990年 | 4篇 |
1989年 | 5篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1986年 | 5篇 |
1985年 | 1篇 |
1984年 | 4篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1974年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有245条查询结果,搜索用时 0 毫秒
1.
2.
3.
4.
Characterization and differential expression of human vascular smooth muscle myosin light chain 2 isoform in nonmuscle cells 总被引:6,自引:0,他引:6
The 20-kDa regulatory myosin light chain (MLC), also known as MLC-2, plays an important role in the regulation of both smooth muscle and nonmuscle cell contractile activity. Phosphorylation of MLC-2 by the enzyme MLC kinase increases the actin-activated myosin ATPase activity and thereby regulates the contractile activity. We have isolated and characterized an MLC-2 cDNA corresponding to the human vascular smooth muscle MLC-2 isoform from a cDNA library derived from umbilical artery RNA. The translation of the in vitro synthesized mRNA, corresponding to the cDNA insert, in a rabbit reticulocyte lysate results in the synthesis of a 20,000-dalton protein that is immunoreactive with antibodies raised against purified chicken gizzard MLC-2. The derived amino acid sequence of the putative human smooth muscle MLC-2 shows only three amino acid differences when compared to chicken gizzard MLC-2. However, comparison with the human cardiac isoform reveals only 48% homology. Blot hybridizations and S1 nuclease analysis indicate that the human smooth muscle MLC-2 isoform is expressed restrictively in smooth muscle tissues such as colon and uterus and in some, but not all, nonmuscle cell lines. Previously reported MLC-2 cDNA from rat aortic smooth muscle cells in culture is ubiquitously expressed in all muscle and nonmuscle cells, and it was suggested that both smooth muscle and nonmuscle MLC-2 proteins are identical and are probably encoded by the same gene. In contrast, the human smooth muscle MLC-2 cDNA that we have characterized from an intact smooth muscle tissue is not expressed in skeletal and cardiac muscles and also in a number of nonmuscle cells.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
5.
D Lundell C Lunn R Greenberg J Fossetta S Narula R Kastelein A Van Kimmenade 《Biotechnology and applied biochemistry》1990,12(5):567-578
The bacterial membrane serves both as a cell organelle and as a barrier for segregating the metabolically active cytoplasm from the extracellular milieu. Thus we can use plasmid vectors designed to produce a hybrid protein containing an efficient signal peptide coupled to the amino terminus of the cloned heterologous protein (secretion cloning vectors) for the production of proteins which are insoluble, proteolytically sensitive, or bacteriocidal when produced in the cytoplasm of Escherichia coli. We demonstrate that human granulocyte-macrophage colony stimulating factor can be isolated as an active species only after transport into the bacterial periplasm. Production of the protein in the bacterial cytoplasm is bacteriocidal. We also demonstrate that biologically active human interleukin 4 appears only after transport of the protein into the bacterial growth medium. The protein forms membrane-associated aggregates in the cytoplasm, and demonstrates an active but nonnative conformation when expressed in the periplasm. This may correlate with the affinity of the interleukin 4 molecule for negatively charged macromolecules, including bacterial membrane components and bacterial lipopolysaccharides, which may alter the folding pathway inside the cell. 相似文献
6.
Summary Six carbamate pesticides namely 1-naphthol, sevin, dimetilan, trematan, NaDDC and dymid were studied to see their effect on
nodulation and nitrogen fixation inPisum sativum andVigna sinensis. Low concentrations of the pesticides have little effect on nodulation and nitrogen fixation, whereas higher concentrations
adversely effect these processes. The results also indicate that then sensitivity depends upon the species of the Rhizobium
and also the type of the pesticide. Pesticides belonging to the carbamate group differ in their capacity to affect nodulation
and nitroge fixation. 相似文献
7.
A Rahier J C Génot F Schuber P Benveniste A S Narula 《The Journal of biological chemistry》1984,259(24):15215-15223
Microsomes from maize seedlings are capable of catalyzing the C-24 alkylation of 4,4,14 alpha-trimethyl-9 beta,19-cyclo-5 alpha-cholest-24-en-3 beta-ol (cycloartenol) by (S)-adenosyl-L-methionine (AdoMet) leading to 24-methylene cycloartanol. Derivatives of cycloartenol bearing a nitrogen atom at C-25 have been previously shown to be potent inhibitors of the AdoMet-cycloartenol-C-24-methyltransferase (Narula, A. S., Rahier, A., Benveniste, P., and Schuber, F. (1981) J. Am. Chem. Soc. 103, 2408-2409). In order to determine the molecular parameters of the inhibition and to gain information about its mechanism, various azasteroids and analogues have been synthesized and assayed. The following results have been obtained. i) The presence of a positive charge at position 25 was found to be the major cause of the inhibition since electrostatically neutral isosteric compounds possessing a carbon in place of the nitrogen atom were not inhibitory. The positive charge leading to inhibition may be conferred by a protonated amine, a quaternary ammonium group, as well as by a sulfonium or an arsonium group. ii) A steroid-like structure of the inhibitor was also important. And iii) the presence of a free 3 beta-hydroxy group and the bent conformation of cycloartenol, which are essential molecular features of the substrate for the methylation reaction, were no longer required to observe inhibition. The data obtained strongly support the idea that C-25 heteroatoms (N, As, and S), substituted triterpenoid derivatives possessing a positive charge at position 25, are analogues of a carbocationic high-energy intermediate involved during the reaction catalyzed by the AdoMet-cycloartenol-C-24-methyltransferase. 相似文献
8.
S.B. Jakowlew P. Khandekar K. Datta H.-H. Arnold S.K. Narula M.A.Q. Siddiqui 《Journal of molecular biology》1982,156(3):673-682
A recombinant DNA plasmid, pMHC8, that contains gene sequences for embryonic chick cardiac myosin heavy chain was constructed, identified and characterized. The identity of the clone was established by hybridization with labeled probes that afford screening of MHC22 with high specificity, by inhibition of MHC synthesis in the in vitro hybrid-arrested translation assay, and by tissue-specific hybridization of labeled pMHC8 DNA to MHC messenger RNA.The pMHC8 DNA probe is highly specific for chick heart muscle tissue, since it hybridized poorly to chick skeletal muscle RNA and did not detectably hybridize to adult rat heart RNA. Upon screening the embryonic chick heart cells in culture, no detectable level of MHC mRNA was observed in dividing myoblasts, but the mRNA appeared in differentiated cardiac myocytes paralleling morphogenetic changes in the embryonic cells. 相似文献
9.
Jatin Machhi Navnit Prajapati Ashutosh Tripathi Zalak S. Parikh Ashish M. Kanhed Kirti Patel Prakash P. Pillai Rajani Giridhar Mange Ram Yadav 《Molecular neurobiology》2017,54(9):6697-6722
Excitotoxicty, a key pathogenic event is characteristic of the onset and development of neurodegeneration. The glutamatergic neurotransmission mediated through different glutamate receptor subtypes plays a pivotal role in the onset of excitotoxicity. The role of NMDA receptor (NMDAR), a glutamate receptor subtype, has been well established in the excitotoxicity pathogenesis. NMDAR overactivation triggers excessive calcium influx resulting in excitotoxic neuronal cell death. In the present study, a series of benzazepine derivatives, with the core structure of 3-methyltetrahydro-3H-benzazepin-2-one, were synthesised in our laboratory and their NMDAR antagonist activity was determined against NMDA-induced excitotoxicity using SH-SY5Y cells. In order to assess the multi-target-directed potential of the synthesised compounds, Aβ1–42 aggregation inhibitory activity of the most potent benzazepines was evaluated using thioflavin T (ThT) and Congo red (CR) binding assays as Aβ also imparts toxicity, at least in part, through NMDAR overactivation. Furthermore, neuroprotective, free radical scavenging, anti-oxidant and anti-apoptotic activities of the two potential test compounds (7 and 14) were evaluated using primary rat hippocampal neuronal culture against Aβ1–42-induced toxicity. Finally, in vivo neuroprotective potential of 7 and 14 was assessed using intracerebroventricular (ICV) rat model of Aβ1–42-induced toxicity. All of the synthesised benzazepines have shown significant neuroprotection against NMDA-induced excitotoxicity. The most potent compound (14) showed relatively higher affinity for the glycine binding site as compared with the glutamate binding site of NMDAR in the molecular docking studies. 7 and 14 have been shown experimentally to abrogate Aβ1–42 aggregation efficiently. Additionally, 7 and 14 showed significant neuroprotective, free radical scavenging, anti-oxidant and anti-apoptotic properties in different in vitro and in vivo experimental models. Finally, 7 and 14 attenuated Aβ1–42-induced tau phosphorylation by abrogating activation of tau kinases, i.e. MAPK and GSK-3β. Thus, the results revealed multi-target-directed potential of some of the synthesised novel benzazepines against excitotoxicity. 相似文献
10.
Targeting of the c-Abl tyrosine kinase to mitochondria in endoplasmic reticulum stress-induced apoptosis 总被引:14,自引:0,他引:14
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Ito Y Pandey P Mishra N Kumar S Narula N Kharbanda S Saxena S Kufe D 《Molecular and cellular biology》2001,21(18):6233-6242
The ubiquitously expressed c-Abl tyrosine kinase localizes to the nucleus and cytoplasm. Using confocal microscopy, we demonstrated that c-Abl colocalizes with the endoplasmic reticulum (ER)-associated protein grp78. Expression of c-Abl in the ER was confirmed by immunoelectron microscopy. Subcellular fractionation studies further indicate that over 20% of cellular c-Abl is detectable in the ER. The results also demonstrate that induction of ER stress with calcium ionophore A23187, brefeldin A, or tunicamycin is associated with translocation of ER-associated c-Abl to mitochondria. In concert with targeting of c-Abl to mitochondria, cytochrome c is released in the response to ER stress by a c-Abl-dependent mechanism, and ER stress-induced apoptosis is attenuated in c-Abl-deficient cells. These findings indicate that c-Abl is involved in signaling from the ER to mitochondria and thereby the apoptotic response to ER stress. 相似文献