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排序方式: 共有361条查询结果,搜索用时 31 毫秒
41.
Zhao H Bernardo MM Osenkowski P Sohail A Pei D Nagase H Kashiwagi M Soloway PD DeClerck YA Fridman R 《The Journal of biological chemistry》2004,279(10):8592-8601
The membrane type (MT)-matrix metalloproteinases (MMPs) constitute a subgroup of membrane-anchored MMPs that are major mediators of pericellular proteolysis and physiological activators of pro-MMP-2. The MT-MMPs also exhibit differential inhibition by members of the tissue inhibitor of metalloproteinase (TIMP) family. Here we investigated the processing, catalytic activity, and TIMP inhibition of MT3-MMP (MMP-16). Inhibitor profile and mutant enzyme studies indicated that MT3-MMP is regulated on the cell surface by autocatalytic processing and ectodomain shedding. Inhibition kinetic studies showed that TIMP-3 is a high affinity inhibitor of MT3-MMP when compared with MT1-MMP (K(i) = 0.008 nm for MT3-MMP versus K(i) = 0.16 nm for MT1-MMP). In contrast, TIMP-2 is a better inhibitor of MT1-MMP. MT3-MMP requires TIMP-2 to accomplish full pro-MMP-2 activation and this process is enhanced in marimastatpretreated cells, consistent with regulation of active enzyme turnover by synthetic MMP inhibitors. TIMP-3 also enhances the activation of pro-MMP-2 by MT3-MMP but not by MT1-MMP. TIMP-4, in contrast, cannot support pro-MMP-2 activation with either enzyme. Affinity chromatography experiments demonstrated that pro-MMP-2 can assemble trimolecular complexes with a catalytic domain of MT3-MMP and TIMP-2 or TIMP-3 suggesting that pro-MMP-2 activation by MT3-MMP involves ternary complex formation on the cell surface. These results demonstrate that TIMP-3 is a major regulator of MT3-MMP activity and further underscores the unique interactions of TIMPs with MT-MMPs in the control of pericellular proteolysis. 相似文献
42.
Naeem lqbal Muhammad Yasin Ashraf Farrukh Javed Muhammad Ashmf Sohail Hameed 《植物学报(英文版)》2006,48(5):558-562
In the present study, the relationship between the nutritional status of leaves and the development of symptoms of cotton leaf curl virus (CLCuV) in two cotton (Gossypium hirsutum L.) cuItlvars (I.e. CIM-240 and S-12) was Investigated. The incidence of disease attack was found to be 100% In the S-12 cuItlvar and 16% in the CIM-240 cuItivar. Geminivirus particles in infected leaves were confirmed by transmission electron microscope examination of highly specific geminivirus coat protein antlsera-treated cell sap. The CLCuV Impaired the accumulation of different nutrients in both cuItivars. A marked decrease in the accumulation of Ca^2+ and K^+ was observed in infected leaves. However, the disease had no effect on leaf concentrations of Na^+, N, and P. It was observed that the curling of leaf margins in CLCuV-Infected plants was associated with the leaf Ca^2+ content; leaf curling was severe in plants with a significant reduction In Ca^2+ content. Moreover, leaf K&+ content was found to be associated with resistance/susceptibility to CLCuV infection. 相似文献
43.
In the present study, the relationship between the nutritional status of leaves and the development of symptoms of cotton leaf curl virus (CLCuV) in two cotton (Gossypium hirsutum L.) cultivars (i.e. CIM-240 and S-12) was investigated. The incidence of disease attack was found to be 100% in the S-12 cultivar and 16% in the CIM-240 cultivar. Geminivirus particles in infected leaves were confirmed by transmission electron microscope examination of highly specific geminivirus coat protein antisera-treated cell sap. The CLCuV impaired the accumulation of different nutrients in both cultivars. A marked decrease in the accumulation of Ca2+ and K+ was observed in infected leaves. However, the disease had no effect on leaf concentrations of Na+, N, and P. It was observed that the curling of leaf margins in CLCuV-infected plants was associated with the leaf Ca2+ content; leaf curling was severe in plants with a significant reduction in Ca2+ content.Moreover, leaf K+ content was found to be associated with resistance/susceptibility to CLCuV infection. 相似文献
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Siddiqui KS Poljak A Guilhaus M De Francisci D Curmi PM Feller G D'Amico S Gerday C Uversky VN Cavicchioli R 《Proteins》2006,64(2):486-501
The cold-adapted alpha-amylase from Pseudoalteromonas haloplanktis (AHA) is a multidomain enzyme capable of reversible unfolding. Cold-adapted proteins, including AHA, have been predicted to be structurally flexible and conformationally unstable as a consequence of a high lysine-to-arginine ratio. In order to examine the role of low arginine content in structural flexibility of AHA, the amino groups of lysine were guanidinated to form homo-arginine (hR), and the structure-function-stability properties of the modified enzyme were analyzed by transverse urea gradient-gel electrophoresis. The extent of modification was monitored by MALDI-TOF-MS, and correlated to changes in activity and stability. Modifying lysine to hR produced a conformationally more stable and less active alpha-amylase. The k(cat) of the modified enzyme decreased with a concomitant increase in deltaH# and decrease in K(m). To interpret the structural basis of the kinetic and thermodynamic properties, the hR residues were modeled in the AHA X-ray structure and compared to the X-ray structure of a thermostable homolog. The experimental properties of the modified AHA were consistent with K106hR forming an intra-Domain B salt bridge to stabilize the active site and decrease the cooperativity of unfolding. Homo-Arg modification also appeared to alter Ca2+ and Cl- binding in the active site. Our results indicate that replacing lysine with hR generates mesophilic-like characteristics in AHA, and provides support for the importance of lysine residues in promoting enzyme cold adaptation. These data were consistent with computational analyses that show that AHA possesses a compositional bias that favors decreased conformational stability and increased flexibility. 相似文献
46.
Bhat SH Azmi AS Hanif S Hadi SM 《The international journal of biochemistry & cell biology》2006,38(12):2074-2081
Several decades back ascorbic acid was proposed as an effective anticancer agent. However, this idea remained controversial and the mechanism of action unclear. In this paper, we show that ascorbic acid at a concentration reported to be achievable through high doses of oral consumption is capable of cytotoxic action against normal cells. Several antioxidants of both animal as well as plant origin including ascorbic acid also possess prooxidant properties. Copper is an essential component of chromatin and can take part in redox reactions. Previously we have proposed a mechanism for the cytotoxic action of plant antioxidants against cancer cells that involves mobilization of endogenous copper ions and the consequent generation of reactive oxygen species. Using human peripheral lymphocytes and Comet assay we show here that ascorbic acid is able to cause oxidatative DNA breakage in normal cells at a concentration of 100–200 μM. Neocuproine, a Cu(I) specific sequestering agent inhibited DNA breakage in a dose dependent manner indicating that Cu(I) is an intermediate in the DNA cleavage reaction. The results are in support of our above hypothesis that involves events that lead to a prooxidant action by antioxidants. The results would support the idea that even a plasma concentration of around 200 μM would be sufficient to cause pharmacological tumor cell death particularly when copper levels are elevated. This would account for the observation of several decades back by Pauling and co-workers where oral doses of ascorbic acid in gram quantities were found to be effective in treating some cancers. 相似文献
47.
Postconditioning attenuates cardiomyocyte apoptosis via inhibition of JNK and p38 mitogen-activated protein kinase signaling pathways 总被引:10,自引:0,他引:10
Sun HY Wang NP Halkos M Kerendi F Kin H Guyton RA Vinten-Johansen J Zhao ZQ 《Apoptosis : an international journal on programmed cell death》2006,11(9):1583-1593
A sequence of intermittent interruptions of oxygen supply (i.e., postconditioning, Postcon) at reoxygenation reduces oxidant-induced
cardiomyocyte loss. This study tested the hypothesis that prevention of cardiomyocyte apoptosis by Postcon is mediated by
mitogen-activated protein kinases pathways. Primary cultured neonatal rat cardiomyocytes were exposed to 3 h hypoxia followed
by 6 h of reoxygenation. Cardiomyocytes were postconditioned by three cycles each of 5 min reoxygenation and 5 min hypoxia
after prolonged hypoxia. Relative to hypoxia alone, reoxygenation stimulated expression of JNKs and p38 kinases, corresponding
to increased activity of JNKs (phospho-c-Jun) and p38 (phospho-ATF2). The level of TNFα in cell lysates, activity of cytosolic
caspases-8, -3, expression of Bax and the number of apoptotic cardiomyocytes were increased while expression of Bcl-2 was
decreased with reoxygenation. Consistent with an attenuation in generation of superoxide anions detected by lucigenin-enhanced
chemiluminescence at early period of reoxygenation, treatment of cardiomyocytes with Postcon further reduced expression and
activity of JNKs and p38 kinases, level of TNFα, the frequency of apoptotic cells and expression of Bax. However, the inhibitory
effects of Postcon on these changes were lost when its application was delayed by 5 min after the start of reoxygenation.
Addition of a JNK/p38 stimulator, anisomycin into cardiomyocytes at the beginning of reoxygenation eliminated protection by
Postcon. These data suggest that 1) hypoxia/reoxygenation elicits cardiomyocyte apoptosis in conjunction with expression and
activation of JNK and p38 kinases, release of TNFα, activation of caspases, and an increase in imbalance of pro-/anti-apoptotic
proteins; 2) Postcon attenuates cardiomyocyte apoptosis, potentially mediated by inhibiting JNKs/p-38 signaling pathways and
reducing TNFα release and caspase expression. 相似文献
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