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31.
Snehlata Chaudhary Ishwar Dutt Vats Madhu Chopra Parbati Biswas Santosh Pasha 《Bioorganic & medicinal chemistry letters》2009,19(15):4364-4366
One of the efficient modes of treatments of chronic hypertension and cardiovascular disorders has been to restrain the formation of angiotensin-II by inhibiting the action of angiotensin-converting enzyme (ACE) on angiotensin-I. The efforts continue towards achieving superior molecules or drugs with improved affinities, better bioavailability and thus to achieve long duration of action with minimum side effects. Previously, we reported a library of tripeptidomimics of Ornithyl–Proline (Orn–Pro) conjugated with various unnatural amino acids and carboxylic acid derived heterocyclics based on the SAR studies of existing ACE inhibitors. Their synthesis and screening for possible inhibitors of angiotensin-converting enzyme (ACE) revealed that increase in the backbone chain length by one carbon atom results in a sudden decrease in their activity. Therefore, in the present study heterocycles with different chain length were introduced to interact with the hydrophobic S2 sub-site of ACE and screened for their in vitro ACE inhibition activity. Further, their binding interaction with C-domain of somatic ACE was also determined. Docking and consequent LUDI scores showed good correlation with binding of these molecules in the active site of ACE. Results suggest that heterocycles with C3 chain length are more appropriate for the effective binding of the tripeptidomimics within the active site of ACE. 相似文献
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The effects of aeration and agitation on the production and molecular weight of poly (γ-glutamic acid) (PGA) were systematically
investigated in batch fermentor cultures of Bacillus licheniformis NCIM 2324. A high aeration rate and agitation speed enhanced the growth of B. licheniformis NCIM 2324, but did not always lead to high PGA production. Additionally, PGA production actually decreased at very high aeration
rates and agitation speeds. The maximum PGA concentration was obtained at 750 rpm and 1 vvm. Rheological studies revealed
that fermentation broth during production of PGA exhibited pseudoplastic behavior. The effects of aeration and agitation on
the molecular weight of PGA were also studied, and the rate and extent of the decrease in the molecular weight of PGA as a
function of time were found to be much greater at high aeration than low aeration. The PGA production of 46.34 g/L with a
specific productivity of 0.17 g-PGA/g-biomass/ h and a PGA yield of 0.48 with respect to total substrate observed in the present
study are much higher than the values reported in previously conducted studies. 相似文献
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Angelini DJ Hyun SW Grigoryev DN Garg P Gong P Singh IS Passaniti A Hasday JD Goldblum SE 《American journal of physiology. Lung cellular and molecular physiology》2006,291(6):L1232-L1245
Tumor necrosis factor (TNF)-alpha is a key mediator of sepsis-associated multiorgan failure, including the acute respiratory distress syndrome. We examined the role of protein tyrosine phosphorylation in TNF-alpha-induced pulmonary vascular permeability. Postconfluent human lung microvascular and pulmonary artery endothelial cell (EC) monolayers exposed to human recombinant TNF-alpha displayed a dose- and time-dependent increase in transendothelial [(14)C]albumin flux in the absence of EC injury. TNF-alpha also increased tyrosine phosphorylation of EC proteins, and several substrates were identified as the zonula adherens proteins vascular endothelial (VE)-cadherin, and beta-catenin, gamma-catenin, and p120 catenin (p120(ctn)). Prior protein tyrosine kinase (PTK) inhibition protected against the TNF-alpha effect. TNF-alpha activated multiple PTKs, including src family PTKs. Prior PTK inhibition with the src-selective agents PP1 and PP2 each protected against approximately 60% of the TNF-alpha-induced increment in [(14)C]albumin flux. PP2 also blocked TNF-alpha-induced tyrosine phosphorylation of VE-cadherin, gamma-catenin, and p120(ctn). To identify which src family kinase(s) was required for TNF-alpha-induced vascular permeability, small interfering RNA (siRNA) targeting each of the three src family PTKs expressed in human EC, c-src, fyn, and yes, were introduced into the barrier function assay. Only fyn siRNA protected against the TNF-alpha effect, whereas the c-src and yes siRNAs did not. These combined data suggest that TNF-alpha regulates the pulmonary vascular endothelial paracellular pathway, in part, through fyn activation. 相似文献
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Raj HG Singh I Kohli E Kumari R Gupta G Tyagi YK Kumar A Prasad AK Kaushik NK Olsen CE Watterson AC Parmar VS 《Bioorganic & medicinal chemistry》2003,11(6):1015-1019
The quantitative structure-activity relationship (QSAR) studies conducted by us earlier revealed the cardinal role of the pyran ring carbonyl group in the acetoxy polyphenolic compounds for the acetoxy polyphenol:protein transacetylase (TAase) activity. Hence, an attempt was made to examine whether such substrate analogues of benzopyran acetates which lack in the pyran ring carbonyl group, such as 7-acetoxy-2,3-dihydro-2,2-dimethylbenzopyran (BPA), cetachin pentaacetate (CPA) and hematoxylin pentaacetate (HPA) could inhibit the 7,8-diacetoxy-4-methylcoumarin (DAMC):protein (glutathione-S-transferase) transacetylase activity. These compounds were indeed found to remarkably inhibit the TAase activity in a concentration dependent manner and exerted their inhibitory action very rapidly. Further BPA, CPA and HPA were found to abolish the TAase mediated activation of NADPH cytochrome C reductase as well as the inhibition of liver microsome catalyzed aflatoxin B(1) (AFB(1))-DNA binding by DAMC very effectively. These results strongly suggest that the acetoxybenzopyrans merit as potent inhibitors of TAase. 相似文献
38.
Adults of the human parasitic trematode Schistosoma mansoni, which causes
hepatosplenic/intestinal complications in humans, synthesize
glycoconjugates containing the Lewis x (Lex) Galbeta1-->4(Fucalpha1--
>3)GlcNAcbeta1-->R, but not sialyl Lewis x (sLex), antigen. We now
report on our analyses of Lexand sLexexpression in S.haematobium and
S.japonicum, which are two other major species of human schistosomes that
cause disease, and the possible autoimmunity to these antigens in infected
individuals. Antigen expression was evaluated by both ELISA and Western
blot analyses of detergent extracts of parasites using monoclonal
antibodies. Several high molecular weight glycoproteins in both S.
haematobium and S. japonicum contain the Lexantigen, but no sialyl
Lexantigen was detected. In addition, sera from humans and rodents infected
with S.haematobium and S.japonicum contain antibodies reactive with Lex.
These results led us to investigate whether Lexantigens are expressed in
other helminths, including the parasitic trematode Fasciola hepatica , the
parasitic nematode Dirofilaria immitis (dog heartworm), the ruminant
nematode Haemonchus contortus , and the free-living nematode Caenorhabditis
elegans . Neither Lexnor sialyl-Lexis detectable in these other helminths.
Furthermore, none of the helminths, including schistosomes, express Lea,
Leb, Ley, or the H- type 1 antigen. However, several glycoproteins from all
helminths analyzed are bound by Lotus tetragonolobus agglutinin , which
binds Fucalpha1-->3GlcNAc, and Wisteria floribunda agglutinin, which
binds GalNAcbeta1-->4GlcNAc (lacdiNAc or LDN). Thus, schistosomes may be
unique among helminths in expressing the Lexantigen, whereas many different
helminths may express alpha1,3-fucosylated glycans and the LDN motif.
相似文献
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