全文获取类型
收费全文 | 109篇 |
免费 | 24篇 |
国内免费 | 2篇 |
专业分类
135篇 |
出版年
2022年 | 1篇 |
2021年 | 2篇 |
2020年 | 1篇 |
2019年 | 1篇 |
2018年 | 1篇 |
2015年 | 5篇 |
2014年 | 5篇 |
2013年 | 2篇 |
2012年 | 4篇 |
2011年 | 4篇 |
2010年 | 6篇 |
2009年 | 10篇 |
2008年 | 2篇 |
2007年 | 13篇 |
2006年 | 3篇 |
2005年 | 13篇 |
2004年 | 7篇 |
2003年 | 5篇 |
2002年 | 10篇 |
2001年 | 5篇 |
2000年 | 5篇 |
1999年 | 2篇 |
1998年 | 4篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1991年 | 1篇 |
1990年 | 3篇 |
1988年 | 1篇 |
1984年 | 1篇 |
1981年 | 2篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
排序方式: 共有135条查询结果,搜索用时 0 毫秒
1.
Analysis of human C8 with monoclonal antibodies. Characterization of a monoclonal antibody that recognizes free C8 alpha-gamma subunit 总被引:1,自引:0,他引:1
The eighth component of human C is essential for the formation of the membranolytic C attack complex. C8 has a unique structure in that two covalently linked chains, C8 alpha and C8 gamma, are associated non-covalently with the third chain, C8 beta. In order to study the structure and assembly of the C8 molecule, a panel of mAb has been produced against the C component C8. Eight of these mAb had reactivity to the C8 alpha-gamma subunit, whereas four reacted with C8 beta. One of the C8 alpha-gamma mAb, C8A2, had specificity for an epitope on the C8 alpha-chain and exhibited no cross-reactivity to any of the other terminal C components, including C8 beta. C8A2 inhibited the hemolytic activity of the C8 alpha-gamma subunit but had no effect on the activity of fluid phase whole C8 or C8 within membrane-bound C5b-8. Functional experiments suggest that C8A2 inhibits C8 alpha-gamma activity by interfering with its interaction with the C8 beta-chain. In an enzyme immunoassay using the C8A2 mAb, free C8 alpha-gamma subunit could be detected in both homozygous and heterozygous C8 beta-deficient serum. However, only low level binding was observed when homozygous C5- and C7-deficient sera were tested. Thus the mAb, C8A2, recognizes an epitope expressed on the C8 alpha-gamma subunit but not on intact C8 and can detect free C8 alpha-gamma in the presence of native C8. 相似文献
2.
3.
Van Lint Johan Van Damme Jo Billiau Alfons Merlevede Wilfried Vandenheede Jackie R. 《Molecular and cellular biochemistry》1993,127(1):171-177
The signal transduction initiated by the human cytokine interleukin-8 (IL-8), the main chemotactic cytokine for neutrophils, was investigated and found to encompass the stimulation of protein kinases. More specifically, IL-8 caused a transient, dose and time dependent activation of a Ser/Thr kinase activity towards myelin basic protein (MBP) and the MBP-derived peptide APRTPGGRR patterned after the specific concensus sequence in MBP for ERK enzymes. The activated MBP kinase was furthermore identified as an extracellular signal regulated kinase (ERK1) based on several criteria such as substrate specificity, molecular weight, activation-dependent mobility shift, and recognition by anti-ERK antibodies. For comparison, the chemotactic response of neutrophils to a stimulus of bacterial origin (fMet-Leu-Phe or fMLP) was also examined and found to involve the activation of a similar ERK enzyme. The present data clearly indicate that in terminally differentiated, non-proliferating human cells, the MBP kinase/ERK activity can serve other purposes than mitogenic signaling, and that processes such as chemotaxis, induced by bacterial peptides as well as by human cytokines like IL-8, involve the regulation of ERK enzyme.Abbreviations IL-8
interleukin-8
- fMLP
fMet-Leu-Phe
- MBP
myelin basic protein
- ERK
extracellular signal regulated kinase
- MAP2
microtubule-associated protein 2
- PK-A
cAMP dependent protein kinase
- PKI
protein kinase inhibitor
- PMSF
phenyl-methanesulfonyl fluoride
- PVDF
poly-vinylidene difluoride
- HBSF
Hank's buffered salt solution
- DAB
3,3-diaminobenzidine tetrahydrochloride
- PNPP
p-nitrophenyl-phosphate
- HSA
human serum albumin
- EGTA
[ethylenebis (oxyethylenenitrilo)]tetraacetic acid
- SDS-PAGE
sodium dodecyl sulfate polyacrylamide gel electrophoresis 相似文献
4.
P Agostinis J Van Lint S Sarno P De Witte J R Vandenheede W Merlevede 《The Journal of biological chemistry》1992,267(14):9732-9737
Treatment of quiescent Swiss 3T3 mouse fibroblasts with bombesin resulted in a rapid 6-8-fold stimulation of cytosolic Ser/Thr kinase activities toward the S6 peptide (RRLSSLR), myelin basic protein (MBP), and the G peptide (SPQPSRRGSESSEE). Anion exchange Mono Q chromatography resolved multiple S6 peptide- and G peptide kinase activities and two MBP kinase peaks. Both MBP- and several S6 peptide kinase peaks could be inactivated by PCSL (PP2A2) phosphatase action. This indicates that the bombesin-induced activation of these enzymes is mediated by a Ser/Thr phosphorylation event. The S6 peptide kinases as well as the two MBP kinases stimulated in response to bombesin are similar to those activated by epidermal growth factor in Swiss 3T3 fibroblasts which suggests that the early events of the signal transduction pathway mediated by these growth factors in Swiss 3T3 cells may converge in the activation of common Ser/Thr kinases. Bombesin, which acts as a sole mitogen for Swiss 3T3 fibroblasts, also produced a several-fold increase in the kinase activity toward the RRREEESEEE peptide, a specific substrate for CK-2. This kinase activity was heparin-sensitive and also measurable with the G peptide (SPQPSRRGSESSEE) and GS-1 peptide (YRRAAVPPSPSPSLSRHSSPHQSEDEE), which contain consensus sequences for phosphorylation by CK-2. The bombesin-stimulated CK-2 activity could not be measured in whole cytosols but was revealed by the anion exchange chromatography step. The activation of CK-2 was not reversed by PCSL phosphatase action. The implication of CK-2 in the signal transduction pathway of bombesin is discussed. 相似文献
5.
J Van Lint P Agostinis V Vandevoorde G Haegeman W Fiers W Merlevede J R Vandenheede 《The Journal of biological chemistry》1992,267(36):25916-25921
Incubation of Swiss 3T3 or L929 cells with tumor necrosis factor (TNF) leads to the rapid stimulation of several cytosolic Ser/Thr kinases active toward myelin basic protein, the S6 peptide (RRLSSLR), the G peptide (SPQPSRRGSESSEE), and Kemptide (LRRASLG). This confirms the hypothesis that kinases other than protein kinases A and C may be involved in the TNF signal transduction. Chromatography on Mono Q resolved multiple kinase peaks with each substrate tested and moreover revealed a TNF-mediated casein kinase-2 activation in both cell lines, measurable with the specific RRREEESEEE peptide or with the G peptide. The TNF-stimulated myelin basic protein kinases-1 and -2 were identified as extracellular signal-regulated kinases-2 and -1, respectively, based on their elution pattern on Mono Q chromatography, their inactivation by protein phosphatase action, their reaction with phosphothreonine and phosphotyrosine antibodies, and by their migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as 42- and 44-kDa proteins recognized by anti-extracellular signal-regulated kinase antibodies. 相似文献
6.
Sturany S Van Lint J Muller F Wilda M Hameister H Hocker M Brey A Gern U Vandenheede J Gress T Adler G Seufferlein T 《The Journal of biological chemistry》2001,276(5):3310-3318
We have isolated the full-length cDNA of a novel human serine threonine protein kinase gene. The deduced protein sequence contains two cysteine-rich motifs at the N terminus, a pleckstrin homology domain, and a catalytic domain containing all the characteristic sequence motifs of serine protein kinases. It exhibits the strongest homology to the serine threonine protein kinases PKD/PKCmicro and PKCnu, particularly in the duplex zinc finger-like cysteine-rich motif, in the pleckstrin homology domain and in the protein kinase domain. In contrast, it shows only a low degree of sequence similarity to other members of the PKC family. Therefore, the new protein has been termed protein kinase D2 (PKD2). The mRNA of PKD2 is widely expressed in human and murine tissues. It encodes a protein with a molecular mass of 105 kDa in SDS-polyacrylamide gel electrophoresis, which is expressed in various human cell lines, including HL60 cells, which do not express PKCmicro. In vivo phorbol ester binding studies demonstrated a concentration-dependent binding of [(3)H]phorbol 12,13-dibutyrate to PKD2. The addition of phorbol 12,13-dibutyrate in the presence of dioleoylphosphatidylserine stimulated the autophosphorylation of PKD2 in a synergistic fashion. Phorbol esters also stimulated autophosphorylation of PKD2 in intact cells. PKD2 activated by phorbol esters efficiently phosphorylated the exogenous substrate histone H1. In addition, we could identify the C-terminal Ser(876) residue as an in vivo phosphorylation site within PKD2. Phosphorylation of Ser(876) of PKD2 correlated with the activation status of the kinase. Finally, gastrin was found to be a physiological activator of PKD2 in human AGS-B cells stably transfected with the CCK(B)/gastrin receptor. Thus, PKD2 is a novel phorbol ester- and growth factor-stimulated protein kinase. 相似文献
7.
Rykx A De Kimpe L Mikhalap S Vantus T Seufferlein T Vandenheede JR Van Lint J 《FEBS letters》2003,546(1):81-86
The protein kinase D family of enzymes consists of three isoforms: PKD1/PKCmu PKD2 and PKD3/PKCnu. They all share a similar architecture with regulatory sub-domains that play specific roles in the activation, translocation and function of the enzymes. The PKD enzymes have recently been implicated in very diverse cellular functions, including Golgi organization and plasma membrane directed transport, metastasis, immune responses, apoptosis and cell proliferation. 相似文献
8.
Wielockx B Staelens J Puimège L Vanlaere I Van Roy M van Lint P Van Roy F Libert C 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(8):5069-5075
In our search for genes that inhibit the inflammatory effects of TNF without diminishing its antitumor capacities we found that, compared with C57BL/6 mice, DBA/2 mice exhibit a dominant resistance to TNF-induced lethality. Tumor-bearing (C57BL/6 x DBA/2)(BXD)F(1) mice completely survived an otherwise lethal TNF/IFN-gamma-antitumor therapy with complete regression of the tumor. This was not the case for C57BL/6 mice. Genetic linkage analysis revealed that TNF resistance is linked to a major locus on distal chromosome 6 and a minor locus on chromosome 17. Compared with littermate controls, chromosome substitution mice carrying a DBA/2 chromosome 6 in a C57BL/6 background were significantly protected against TNF and TNF/IFN-gamma, albeit less so than DBA/2 mice. Definition of a critical region of 13 Mb on chromosome 6 was the highest mapping resolution obtained. Further analysis of candidate genes may provide a powerful tool to control TNF-induced pathologies in humans. 相似文献
9.
10.
von Blume J Knippschild U Dequiedt F Giamas G Beck A Auer A Van Lint J Adler G Seufferlein T 《The EMBO journal》2007,26(22):4619-4633
Protein kinase D2 (PKD2), a member of the PKD family of serine/threonine kinases, is localized in various subcellular compartments including the nucleus where the kinase accumulates upon activation of G-protein-coupled receptors. We define three critical post-translational modifications required for nuclear accumulation of PKD2 in response to activation of the CCK2 receptor (CCK2R): phosphorylation at Ser706 and Ser710 within the activation loop by PKC eta leading to catalytic activity and phosphorylation at Ser244 within the zinc-finger domain, which is crucial for blocking nuclear export of active PKD2 by preventing its interaction with the Crm-1 export machinery. We identify CK1delta and epsilon as upstream activated kinases by CCK2R that phosphorylate PKD2 at Ser244. Moreover, nuclear accumulation of active PKD2 is a prerequisite for efficient phosphorylation of its nuclear substrate, HDAC7. Only nuclear, active PKD2 mediates CCK2R-induced HDAC7 phosphorylation and Nur77 expression. Thus, we define a novel, compartment-specific signal transduction pathway downstream of CCK2R that phosphorylates PKD2 at three specific sites, results in nuclear accumulation of the active kinase and culminates in efficient phosphorylation of nuclear PKD2 substrates in human gastric cancer cells. 相似文献