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排序方式: 共有3251条查询结果,搜索用时 31 毫秒
1.
基于有限变形理论中的能量原理和变分原理,考虑以有裂纹的瞬时位形为参考,建立增量变形引起的裂纹扩展方程能够更真实的描述裂纹尖端的扩展机制,在含有裂纹物体的瞬时变形的基础上,推导了裂纹体的能量释放率和增率的形式,提出了裂纹扩展判据.该判据反映了单位时间内裂纹扩展单位面积可以提供的能量与单位时间内裂纹扩展单位面积所需要的能量... 相似文献
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Three new triterpene lactones, lancilactones A (1), B (2), and C (3), together with the known kadsulactone A (4), were isolated from the stems and roots of Kadsura lancilimba. Their structures and stereochemistries were determined primarily from mass and NMR spectral data. Compound 3 inhibited HIV replication with an EC50 value of 1.4 microg/mL and a therapeutic index of greater than 71.4. 相似文献
4.
R Lewis S Kapur C Jones J DaSilva GM Brown AA Wilson S Houle RB Zipursky 《Canadian Metallurgical Quarterly》1999,156(1):72-78
BACKGROUND: In the FRISC trial, dalteparin 120 IU/kg body weight twice daily for unstable coronary artery disease was safe and reduced the risk of new coronary events. This risk reduction was maintained during the following extended treatment with a fixed dose of 7500 IU dalteparin once daily. METHODS AND RESULTS: Minor bleeding was more frequent in women compared with men: relative risk (CI) 2.88 (1.78 to 4.67) during the weight-adjusted and 2.36 (1.37 to 2.63) during the fixed dose treatment. The anti-Xa activity determined in samples (n = 175) obtained during the acute phase treatment was higher in women compared with men (P <.001) and in nonsmokers compared with smokers (<.001) in multiple regression analysis. Also, during the fixed-dose treatment (n = 131) an independent relation between anti-Xa activity and sex (P <.001), but not smoking habits, persisted. CONCLUSION: To improve future low-molecular-weight heparin dose regimens for the treatment of acute coronary syndromes, it might be important to consider the influence of sex and smoking habits. 相似文献
5.
Dougan DA; Malby RL; Gruen LC; Kortt AA; Hudson PJ 《Protein engineering, design & selection : PEDS》1998,11(1):65-74
The interactions between the Fab and single-chain Fv (scFv) fragments of an
antibody (NC10) and its antigen, influenza virus neuraminidase, were
analysed in the crystal structures of the Fab-neuraminidase and
scFv-neuraminidase complexes. To investigate the contribution to binding
made by cavities, salt links and hydrogen bonds in the antibody- antigen
interface, 14 single amino acid replacements were made at six contact
residues in the scFv fragment by site-directed mutagenesis. The binding
affinity of each mutant scFv antibody for neuraminidase was determined with
a BIAcore optical biosensor. Four of the mutations resulted in large
changes in the free energy of binding to neuraminidase (deltadeltaG > 1
kcal/mol) and together may account for approximately 70% of the free energy
of binding. Hence these data support the theory that a small number of
residues form the 'functional epitope' and are most important for binding
of NC10 to neuraminidase. The salt link between antibody residue (Asp)H56
and (Lys)N432 from neuraminidase was demonstrated to be important for
affinity, since substitution of (Asp)H56 with Asn caused a large reduction
in the free energy of binding (deltadeltaG = +2.8 kcal/mol). Hydrogen bonds
provided by (Tyr)L32 and (Asp)H56 were also important for binding: mutation
of (Tyr)L32 to Phe resulted in a significant reduction in binding affinity
(deltadeltaG = +1.7 kcal/mol). Disruption of hydrophobic interactions (van
der Waals contacts) led to significant reductions in affinity also
((Tyr)H99 to Ala, deltadeltaG = +1.5 kcal/mol; (Leu)L94 to Ala, deltadeltaG
> +3.0 kcal/mol). An attempt to increase binding affinity by filling a
cavity in the interface with a larger antibody side chain was unsuccessful,
as the free energy gained by new antibody-antigen interactions did not
compensate for the removal of cavity-bound water molecules.
相似文献
6.
JA Robl R Sulsky E Sieber-McMaster DE Ryono MP Cimarusti LM Simpkins DS Karanewsky S Chao MM Asaad AA Seymour M Fox PL Smith NC Trippodo 《Canadian Metallurgical Quarterly》1999,42(2):305-311
A series of 7-(di)alkyl and spirocyclic substituted azepinones were generated and incorporated as conformationally restricted dipeptide surrogates in mercaptoacyl dipeptides. Clear structure-activity relationships with respect to both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) activity in vitro were observed. The best in this series, compound 1g, a geminally dimethylated C-7-substituted azepinone, demonstrated excellent blood pressure lowering in animal models. Compound 1g (BMS-189921) is characterized by a good duration of activity and excellent oral efficacy in models relevant to ACE or NEP inhibition, and its activity is comparable to that of the clinically efficacious agent omapatrilat. Consequently this inhibitor has been advanced clinically for the treatment of hypertension and congestive heart failure. 相似文献
7.
DV Stambolsky YS Kuzmenko MP Philippova VN Bochkov ZD Bespalova AA Azmuko NM Kashirina TN Vlasik VA Tkachuk TJ Resink 《Canadian Metallurgical Quarterly》1999,1416(1-2):155-160
Atypical cell surface lipoprotein-binding proteins of 105 kDa and 130 kDa are present in membranes of vascular smooth muscle cells. We recently identified the 105 kDa protein from human aortic media as T-cadherin, an unusual glycosylphosphatidylinositol (GPI)-anchored member of the cadherin family of cell adhesion proteins. The goal of the present study was to determine the identity of 130 kDa lipoprotein-binding protein of smooth muscle cells. We applied different approaches that included protein sequencing of purified protein from human aortic media, the use of human T-cadherin peptide-specific antisera, and enzymatic treatment of cultured cells with trypsin and GPI-specific phospholipase C. Our results indicate that the 130 kDa protein is a partially processed form of T-cadherin which is attached to the membrane surface of smooth muscle cells via a GPI anchor and contains uncleaved N-terminal propeptide sequence. Our data disclose that, in contrast to classical cadherins, T-cadherin is expressed on the cell surface in both its precursor (130 kDa) and mature (105 kDa) forms. 相似文献
8.
Histories of deliveries and development records of 44 newborns with penumopathies who had died on the first days of life in the presence of phenomena of the syndrome of respiratory disorder were analysed and the newborns' lungs were morphologically investigated. The investigation made it possible to single out the following forms of pneumopathy in newborns: edematous-hemorrhagic, hyaline, atelectatic, aspirated, and mixed. In the majority of cases the syndrome of respiratory disorder was a sequela of hypoxia of the intrauterine origin which continued during the first hours and days of life after birth. Such "primary asphyxia" may lead to the development of pneumopathy in a neonate. On the other hand, "secondary asphyxia" in many cases represent sequelae of penumopathy destructural and functional immaturity of the pulmonary tissue, hypoxia, a higher permeability of vessels of the microcirculatory bed, spasm of small pulmonary arteris contributed considerably to the development of penumopathies. 相似文献
9.
A Parashar AA Akhand R Rawar T Furuno M Nakanishi M Kato H Suzuki I Nakashima 《Canadian Metallurgical Quarterly》1999,26(1-2):227-231
The mechanism of the lymphocyte stimulatory action of sulfhydryl group-reactive mercuric ions was studied with respect to its potential ability to induce a protein tyrosine phosphorylation-linked signal for mobilization of free Ca2+ into cytoplasm and nucleus of the cell. Exposure of human leukamic T cell line (Jurkat) cells to high (1 mM) and low (0.01 mM) concentrations of HgCl2 induced tyrosine phosphorylation of multiple proteins in a concentration-dependent manner. Confocal microscopy directly visualized the time course localization of Ca2+ inside the cells after exposure to HgCl2. The onset and level of Ca2+ mobilization following HgCl2 exposure were in parallel to those of protein tyrosine phosphorylation. Interestingly, by either concentration of HgCl2, Ca2+ was mobilized in both cytoplasm and nucleus almost simultaneously, and the level of Ca2+ mobilization in the nucleus was more than that in the cytoplasm. All the HgCl2-mediated Ca2+ mobilization was prevented by addition of protein kinase inhibitor staurosporin prior to HgCl2. These results suggest that heavy metal stress triggers a protein tyrosine phosphorylation-linked signal that leads to a nuclear event-dominant Ca2+ mobilization. 相似文献
10.
IS Efimova A Salminen P Pohjanjoki J Lapinniemi NN Magretova BS Cooperman A Goldman R Lahti AA Baykov 《Canadian Metallurgical Quarterly》1999,274(6):3294-3299
Recent crystallographic studies on Escherichia coli inorganic pyrophosphatase (E-PPase) have identified three Mg2+ ions/enzyme hexamer in water-filled cavities formed by Asn24, Ala25, and Asp26 at the trimer-trimer interface (Kankare, J., Salminen, T., Lahti, R., Cooperman, B., Baykov, A. A., and Goldman, A. (1996) Biochemistry 35, 4670-4677). Here we show that D26S and D26N substitutions decrease the stoichiometry of tight Mg2+ binding to E-PPase by approximately 0.5 mol/mol monomer and increase hexamer stability in acidic medium. Mg2+ markedly decelerates the dissociation of enzyme hexamer into trimers at pH 5.0 and accelerates hexamer formation from trimers at pH 7.2 with wild type E-PPase and the N24D variant, in contrast to the D26S and D26N variants, when little or no effect is seen. The catalytic parameters describing the dependences of enzyme activity on substrate and Mg2+ concentrations are of the same magnitude for wild type E-PPase and the three variants. The affinity of the intertrimer site for Mg2+ at pH 7.2 is intermediate between those of two Mg2+ binding sites found in the E-PPase active site. It is concluded that the metal ion binding site found at the trimer-trimer interface of E-PPase is a high affinity site whose occupancy by Mg2+ greatly stabilizes the enzyme hexamer but has little effect on catalysis. 相似文献