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31.
Structure of an intermolecular electron-transfer complex: p-cresol methylhydroxylase at 6.0-A resolution 总被引:1,自引:1,他引:0 下载免费PDF全文
N Shamala L W Lim F S Mathews W McIntire T P Singer D J Hopper 《Proceedings of the National Academy of Sciences of the United States of America》1986,83(13):4626-4630
The structure of p-cresol methylhydroxylase [4-cresol:(acceptor) oxidoreductase (methyl-hydroxylating), EC 1.17.99.1], a flavocytochrome c, has been determined at 6.0-A resolution. The structure analysis is based on two heavy-atom derivatives with anomalous scattering and 2-fold averaging about a noncrystallographic axis. The molecule is an alpha 2 beta 2 tetramer with a cytochrome subunit of Mr approximately 8500 and a flavoprotein subunit of Mr approximately 49,000. The flavoprotein subunits are tightly packed about the molecular 2-fold axis, whereas the cytochrome subunits are located on the outside of the molecule, each in a depression on the surface of a flavoprotein subunit. The results of this study have led to the following conclusions. The alpha 2 beta 2 quaternary structure of the enzyme is different from alpha beta as originally thought. The orientation of the cytochrome subunit and the surface complementarity of the cytochrome and flavoprotein subunits are clearly defined. The cytochrome subunit is similar in size to other small bacterial cytochromes but probably forms a distinct subclass. The titration (by substrate) behavior of the enzyme and other kinetic properties are rationalized by its quaternary structure. 相似文献
32.
Abstract: The crystal structures of the peptides, Boc‐Leu‐Trp‐Val‐OMe ( 1) , Ac‐Leu‐Trp‐Val‐OMe ( 2a and 2b), Boc‐Leu‐Phe‐Val‐OMe ( 3 ), Ac‐Leu‐Phe‐Val‐OMe ( 4 ), and Boc‐Ala‐Aib‐Leu‐Trp‐Val‐OMe ( 5 ) have been determined by X‐ray diffraction in order to explore the nature of interactions between aromatic rings, specifically the indole side chain of Trp residues. Peptide 1 adopts a type I β‐turn conformation stabilized by an intramolecular 4→1 hydrogen bond. Molecules of 1 pack into helical columns stabilized by two intermolecular hydrogen bonds, Leu(1)NH…O(2)Trp(2) and IndoleNH…O(1)Leu(1). The superhelical columns further pack into the tetragonal space group P43 by means of a continuous network of indole–indole interactions. Peptide 2 crystallizes in two polymorphic forms, P21 ( 2a ) and P212121 ( 2b ). In both forms, the peptide backbone is extended, with antiparallel β‐sheet association being observed in crystals. Extended strand conformations and antiparallel β‐sheet formation are also observed in the Phe‐containing analogs, Boc‐Leu‐Phe‐Val‐OMe ( 3 ) and Ac‐Leu‐Phe‐Val‐OMe ( 4 ). Peptide 5 forms a short stretch of 310‐helix. Analysis of aromatic–aromatic and aromatic–amide interactions in the structures of peptides, 1 , 2a , 2b are reported along with the examples of 14 Trp‐containing peptides from the Cambridge Crystallographic Database. The results suggest that there is no dramatic preference for a preferred orientation of two proximal indole rings. In Trp‐containing peptides specific orientations of the indole ring, with respect to the preceding and succeeding peptide units, appear to be preferred in β‐turns and extended structures. 相似文献
33.
Brandon J. Sumpio Gautham Chitragari Takeshi Moriguchi Sherif Shalaby Valeria Pappas-Brown Asif M. Khan Shamala Devi Sekaran Bauer E. Sumpio Dennis J. Grab 《The International journal of angiology》2015,24(1):41-46
African trypanosomes are tsetse fly transmitted protozoan parasites responsible for
human African trypanosomiasis, a disease characterized by a plethora of neurological
symptoms and death. How the parasites under microvascular shear stress (SS) flow
conditions in the brain cross the blood–brain barrier (BBB) is not known. In vitro
studies using static models comprised of human brain microvascular endothelial cells
(BMEC) show that BBB activation and crossing by trypanosomes requires the orchestration
of parasite cysteine proteases and host calcium-mediated cell signaling. Here, we
examine BMEC barrier function and the activation of extracellular signal-regulated
kinase (ERK)1/2 and ERK5, mitogen-activated protein kinase family regulators of
microvascular permeability, under static and laminar SS flow and in the context of
trypanosome infection. Confluent human BMEC were cultured in electric cell-substrate
impedance sensing (ECIS) and parallel-plate glass slide chambers. The human BMEC were
exposed to 2 or 14 dyn/cm2 SS in the presence or absence of trypanosomes.
Real-time changes in transendothelial electrical resistance (TEER) were monitored and
phosphorylation of ERK1/2 and ERK5 analyzed by immunoblot assay. After reaching
confluence under static conditions human BMEC TEER was found to rapidly increase when
exposed to 2 dyn/cm2 SS, a condition that mimics SS in brain postcapillary
venules. Addition of African trypanosomes caused a rapid drop in human BMEC TEER.
Increasing SS to 14 dyn/cm2, a condition mimicking SS in brain capillaries,
led to a transient increase in TEER in both control and infected human BMEC. However, no
differences in ERK1/2 and ERK5 activation were found under any condition tested. African
trypanosomiasis alters BBB permeability under low shear conditions through an ERK1/2 and
ERK5 independent pathway. 相似文献
34.
Mohammed Abdelfatah Alhoot Alwin Kumar Rathinam Seok Mui Wang Rishya Manikam Shamala Devi Sekaran 《International journal of medical sciences》2013,10(6):719-729
Despite the importance of DENV as a human pathogen, there is no specific treatment or protective vaccine. Successful entry into the host cells is necessary for establishing the infection. Recently, the virus entry step has become an attractive therapeutic strategy because it represents a barrier to suppress the onset of the infection. Four putative antiviral peptides were designed to target domain III of DENV-2 E protein using BioMoDroid algorithm. Two peptides showed significant inhibition of DENV when simultaneously incubated as shown by plaque formation assay, RT-qPCR, and Western blot analysis. Both DET4 and DET2 showed significant inhibition of virus entry (84.6% and 40.6% respectively) using micromolar concentrations. Furthermore, the TEM images showed that the inhibitory peptides caused structural abnormalities and alteration of the arrangement of the viral E protein, which interferes with virus binding and entry. Inhibition of DENV entry during the initial stages of infection can potentially reduce the viremia in infected humans resulting in prevention of the progression of dengue fever to the severe life-threatening infection, reduce the infected vector numbers, and thus break the transmission cycle. Moreover these peptides though designed against the conserved region in DENV-2 would have the potential to be active against all the serotypes of dengue and might be considered as Hits to begin designing and developing of more potent analogous peptides that could constitute as promising therapeutic agents for attenuating dengue infection. 相似文献
35.
Ramapraba Appanna Seok Mui Wang Sasheela A. Ponnampalavanar Lucy Chai See Lum Shamala Devi Sekaran 《The American journal of tropical medicine and hygiene》2012,87(5):936-942
Plasma leakage in severe dengue has been postulated to be associated with skewed cytokine immune responses. In this study, the association of cytokines with vascular permeability in dengue patients was investigated. Human serum samples collected from 48 persons (13 with dengue fever, 29 with dengue hemorrhagic fever, and 6 healthy) were subjected to cytokines analysis by using Luminex Multiplex Technology. Selected serum samples from patients with dengue hemorrhagic fever sera and recombinant human cytokines were then tested for roles on inducing vascular permeability by treatment of human umbilical vein endothelial cells. Confocal immunofluorescence staining indicated morphologic alteration of human umbilical vein endothelial cells treated with serum samples from patients with dengue hemorrhagic fever compared with serum samples from healthy persons. The findings suggest that cytokines produced during dengue hemorrhagic infections could induce alterations in the vascular endothelium, which may play a fundamental role in the pathophysiology of dengue. 相似文献
36.
37.
Osman O Fong MY Devi S 《The Southeast Asian journal of tropical medicine and public health》2008,39(1):62-78
A preliminary study of dengue infection in Brunei between 2005 and 2006 showed that dengue 2 was the predominant serotype. A total of five DEN-2 isolates were isolated and maintained in the mosquito cell-line, albopictus C6/36. The sequence spanning the envelope and non-structural protein 1 (E/NS1) junction (positions 2311 to 2550) of the isolates were determined and analysed at the amino acid and nucleotide levels. Alignment of the 240 nucleotide sequences among the five isolates showed changes occurring at 7 positions (2.9%) of the region. All but one nucleotide substitution (position 2319, amino acid 742 V --> F) were found at the 3rd position of the codons and were silent mutations. Amino acid homology ranged from 98% to 100%. Sequence divergence of the Brunei isolates varied from 5% to 6.6% compared with dengue-2 prototype New Guinea C strain. Comparison of the Brunei DEN-2 isolates with sixty-five other strains placed them in a cluster containing Indonesian strains isolated in 1973, 1978 and 2004 and Malaysian strains isolated in 1996, 1998 and 1999 in genotype group IV. 相似文献
38.
Prema G. Vasudev Subrayashastry Aravinda Kuppanna Ananda Shettykere Dayananda Veena Kuppuswamy Nagarajan Narayanaswamy Shamala Padmanabhan Balaram 《Chemical biology & drug design》2009,73(1):83-96
Gabapentin, a widely used antiepileptic drug, crystallizes in multiple polymorphic forms. A new crystal form of gabapentin monohydrate in the space group Pbca is reported and the packing arrangement compared with that of a previously reported polymorph in the space group P21/c [Ibers, J.A. (2001) Acta Crystallogr; C57:641]. Gabapentin polymorphs can also occur from a selection of one of the two distinct chair forms of the 1,1‐disubstituted cyclohexane. Crystal structures of the E and Z isomers of 4‐tert‐butylgabapentin provide models for analyzing anticipated packing modes in the conformational isomers of gabapentin. The E isomer crystallized in the space group Pca21, while the Z isomer crystallized in the space group P21/c. The crystal structure of E‐4‐tert‐butylgabapentin provides the only example of a structure in a non‐centrosymmetric space group. Crystal structures of the hydrochloride and hydrobromide salts of 4‐tert‐butyl derivatives are reported. The results suggest that for gabapentin, a large ‘polymorph‐space’ may be anticipated, in view of the multiple conformational states that are accessible to the molecule. 相似文献
39.
40.
Mimotopes of the Vi antigen of Salmonella enterica serovar typhi identified from phage display peptide library 总被引:2,自引:0,他引:2
Tang SS Tan WS Devi S Wang LF Pang T Thong KL 《Clinical and diagnostic laboratory immunology》2003,10(6):1078-1084
The capsular polysaccharide Vi antigen (ViCPS) is an essential virulence factor and also a protective antigen of Salmonella enterica serovar Typhi. A random 12-mer phage-displayed peptide library was used to identify mimotopes (epitope analogues) of this antigen by panning against a ViCPS-specific monoclonal antibody (MAb) ATVi. Approximately 75% of the phage clones selected in the fourth round carried the peptide sequence TSHHDSHGLHRV, and the rest of the clones harbored ENHSPVNIAHKL and other related sequences. These two sequences were also obtained in a similar panning process by using pooled sera from patients with a confirmed diagnosis of typhoid fever, suggesting they mimic immunodominant epitopes of ViCPS antigens. Binding of MAb ATVi to the mimotopes was specifically blocked by ViCPS, indicating that they interact with the same binding site (paratope) of the MAb. Data and reagents generated in this study have important implications for the development of peptide-base diagnostic tests and peptide vaccines and may also provide a better understanding of the pathogenesis of typhoid fever. 相似文献