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排序方式: 共有283条查询结果,搜索用时 31 毫秒
221.
222.
Balu K. Vidya Rajendran Rao Sethumadhavan Rituraj Purohit 《Cell biochemistry and biophysics》2013,67(2):623-633
Members of the novel SH2-containing protein (NSP3) and Crk-associated substrate (p130Cas) protein families form a multi-domain signalling platforms that mediate cell signalling process. We analysed the damaging consequences of three mutations, each from NSP3 (NSP3L469R, NSP3L623E, NSP3R627E) and p130Cas (p130CasF794R, p130CasL787E, p130CasD797R) protein with respect to their native biological partners. Mutations depicted notable loss in interaction affinity towards their corresponding biological partners. NSP3L469R and p130CasD797R mutations were predicted as most prominent in docking analysis. Molecular dynamics (MD) studies were conducted to evaluate structural consequences of most prominent mutation in NSP3 and p130Cas obtained from the docking analysis. MD analysis confirmed that mutation in NSP3L469R and p130CasD797R showed significant structural deviation, changes in conformations and increased flexibility, which in turn affected the binding affinity with their biological partners. Moreover, the root mean square fluctuation has indicated a rise in fluctuation of residues involved in moderate interaction acquired between the NSP3 and p130Cas. It has significantly affected the binding interaction in mutant complexes. The results obtained in this work present a detailed overview of molecular mechanisms involved in the loss of cell signalling associated with NSP3 and p130Cas protein. 相似文献
223.
Regueiro-Ren A Carroll TM Chen Y Matson JA Huang S Mazzucco CE Stickle TM Vyas DM Balasubramanian BN 《Bioorganic & medicinal chemistry letters》2002,12(23):3403-3405
Core-modified sordaricin derivatives were prepared via biotransformation followed by chemical modification and tested for antifungal activity. The antifungal activity proved to be very sensitive to modifications in the sterics and/or lipophilicity of the diterpene skeleton. Introduction of polar groups such as hydroxyl in the diterpene core results in loss of potency while small and lipophilic groups such as fluorine and the 7,8-olefin are well tolerated. 相似文献
224.
225.
Mahlum E Mandal D Halder C Maran A Yaszemski MJ Jenkins RB Bolander ME Sarkar G 《Analytical biochemistry》2007,365(2):215-221
Noncovalent protein delivery into cells via peptide carriers is an emerging concept. Only a handful of such peptides are known. To address various limitations associated with protein delivery for therapeutic purposes, a greater number of different delivery peptides would be required. No general method exists for creating such peptides. By combining a sequence of 16 lysine residues (K16) with the signal peptide (SP) sequence of Kaposi's fibroblast growth factor (K-FGF), we have synthesized a peptide (K16SP) that efficiently and noncovalently delivers functionally intact proteins (immunoglobulin G molecules, beta-galactosidase, and green fluorescent protein) into mammalian cells. The peptides K16 and SP each alone did not show any noncovalent protein-carrying capacity. K16SP appears to be nontoxic to cells and three to four times more efficient than a commercially available peptide reagent. Our approach offers proof-of-concept of a general strategy for creating a diverse array of peptide carriers for eventual therapeutic applications. 相似文献
226.
Wittman MD Balasubramanian B Stoffan K Velaparthi U Liu P Krishnanathan S Carboni J Li A Greer A Attar R Gottardis M Chang C Jacobson B Sun Y Hansel S Zoeckler M Vyas DM 《Bioorganic & medicinal chemistry letters》2007,17(4):974-977
A novel class of 1H-(benzimidazol-2-yl)-1H-pyridin-2-one inhibitors of insulin-like growth factor I (IGF-1R) kinase is described. This report discusses the SAR of 4-(2-hydroxy-2-phenylethylamino)-substituted pyridones with improved IGF-1R potency. 相似文献
227.
Webb MA Platton SL Dennison AR James RF 《In vitro cellular & developmental biology. Animal》2007,43(7):210-214
Islet cells derived from patients with persistent hyperinsulinemic hypoglycemia of infancy (PHHI) have the ability to grow
readily in simple culture media. However, as with primary islets and cell lines, they lose hormone expression upon growth.
In this study, we have investigated the role of three-dimensional cell-to-cell contact in the reinitiation of hormone expression
in growth dedifferentiated PHHI-derived cells. Two main methods of cell aggregation were studied; the promotion of pseudoislets
through petri dish culture and the creation of cell aggregates in the microgravity environment of the high aspect ratio vessel
(HARV). Immunohistochemical analysis and ELISA assay showed that petri dish culture did not re-establish endocrine expression
in any of the five cultures tested. However, through HARV technology, we have demonstrated that it is possible to reactivate
insulin, glucagon, somatostatin, and GAD expression in PHHI-derived cells that had previously stopped expressing these markers.
These results indicate that the unique environment of the HARV can be conducive to the upregulation of endocrine expression
of islet-derived cells and optimization of culture conditions may prove useful in the sphere of β cell proliferation. 相似文献
228.
Junlan Zhang Yiqun Ling Liping Tang Bao Luo Balu K Chacko Rakesh P Patel Michael B Fallon 《Journal of applied physiology》2007,102(3):949-955
Hepatopulmonary syndrome (HPS) following rat common bile duct ligation results from pulmonary molecular changes that may be influenced by circulating TNF-alpha and increased vascular shear stress, through activation of NF-kappaB or Akt. Increased pulmonary microvascular endothelin B (ET(B)) receptor and endothelial nitric oxide synthase (eNOS) levels contribute to nitric oxide production and the development of experimental HPS. Pentoxifylline (PTX), a phosphodiesterase and nonspecific TNF-alpha inhibitor, ameliorates experimental HPS when begun before hepatic injury. However, how PTX influences the molecular events associated with initiation of experimental HPS after liver injury is established is unknown. We assessed the effects of PTX on the molecular and physiological features of HPS in vivo and on shear stress or TNF-alpha-mediated events in rat pulmonary microvascular endothelial cells in vitro. PTX significantly improved HPS without altering portal or systemic hemodynamics and downregulated pulmonary ET(B) receptor levels and eNOS expression and activation. These changes were associated with a reduction in circulating TNF levels and NF-kappaB activation and complete inhibition of Akt activation. In rat pulmonary microvascular endothelial cells, PTX inhibited shear stress-induced ET(B) receptor and eNOS expression and eNOS activation. These effects were also associated with inhibition of Akt activation and were reproduced by wortmanin. In contrast, TNF-alpha had no effects on endothelial ET(B) and eNOS alterations in vitro. PTX has direct effects in the pulmonary microvasculature, likely mediated through Akt inhibition, that ameliorate experimental HPS. 相似文献
229.
mTOR is the rapamycin-sensitive kinase that confers mechanically-induced phosphorylation of the hydrophobic motif site Thr(389) in p70(S6k) 总被引:2,自引:0,他引:2
Mechanical stretch induces phosphorylation of the hydrophobic motif site Thr(389) in p70(S6k) through a rapamycin-sensitive (RS) pathway that involves a unique PI3K-independent mechanism. Rapamycin is considered to be a highly specific inhibitor of the protein kinase mTOR; however, mTOR is also considered to be a PI3K-dependent signaling molecule. Thus, questions remain as to whether mTOR is the RS element that confers mechanically-induced signaling to p70(S6k)(389). In this study, rapamycin-resistant mutants of mTOR along with mechanical stretch were used to address this question. The results indicate that mTOR is the RS element and reveal that mTOR signaling can be activated through a PI3K-independent mechanism. 相似文献
230.
František Baluška Monika Polsakiewicz Mechthild Peters Dieter Volkmann 《Protoplasma》2000,212(3-4):137-145
Summary Using a heterologous myosin antibody raised against the whole molecule of bovine muscle myosin, we have identified a myosin-like protein in maize. Immunoblots of subcellular fractions isolated from roots identified one distinct band at about 210 kDa in the microsomal protein fraction and one band at about 180 kDa in the soluble protein fraction. Indirect immunofluorescence was performed using maize root apex sections to reveal endocellular distributions of the myosin-like protein. Both diffuse and particulate labelling patterns were observed throughout the cytoplasm of all root cells. In mitotic cells, myosin-like protein was excluded from spindle regions. Amyloplast surfaces were labelled prominently in cells of the root cap statenchyma and in all root cortex cells. On the other hand, myosin-like protein was prominently enriched at cellular peripheries in cells of the pericycle and outer stele in the form of continuous peripheral labelling. From all root apex tissues, phloem elements showed the most abundant presence of myosinlike protein.Abbreviations AFs
actin filaments
- MTs
microtubules
Dedicated to Professor Walter Gustav Url on the occasion of his 70th birthday 相似文献