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131.
H. Belfrage Mikael Dohlsten Gunnar Hedlund Terje Kalland 《Cancer immunology, immunotherapy : CII》1997,44(2):77-82
Injection of the superantigen staphylococcal enterotoxin A (SEA) activates both CD4+ and CD8+ T cells expressing certain families of T cell receptor (TCR) variable-region β (Vβ) chain. T cells respond with profound cytokine production and induction of cytotoxicity. Repeated injections, however, cause
deletion and anergy of both CD4+ and CD8+ T cells, resulting in reduced frequency of SEA-responsive cells TCR-Vβ11+ as well as reduced cytokine levels in serum upon challenge with SEA. Exogenous interleukin-2 (IL-2) in vivo rescued SEA-responsive
CD4+ and CD8+ cells from SEA-induced deletion and/or increase expansion of SEA-primed cells as well as preventing down-regulation of endogenous
IL-2 production in vivo. Combined treatment with SEA and IL-2 also superinduced production of important cytokines for the
cytotoxic function of T cells, tumour necrosis factor α, interferon γ and IL-6, on a cellular level. These studies show that
continuous stimulation with IL-2 in vivo could be useful for superantigen-based immunotherapy by induction of excessive T
cell activation and by prevention of the development of T cell deletion and anergy.
Received: 29 August 1996 / Accepted: 16 January 1997 相似文献
132.
To distinguish the mass loading effect from the total frequency change is a problem in the application of a quartz crystal microbalance (QCM) biosensor in the liquid phase. Based on the characteristic damping theory, this paper proposes a new method of dual modulation to solve this problem. Usingg polyethyleneimine to immobilize anti-SE (staphylococcin enterotoxin) antibody (C2 type), a dual modulated QCM SE biosensor was developed and the experiment proved that it has little cross-reaction with B-type SE. The measuring curve of the sensor was also determined through experiment. 相似文献
133.
Crystal structure of heat-labile enterotoxin from Escherichia coli with increased thermostability introduced by an engineered disulfide bond in the A subunit. 总被引:2,自引:1,他引:1
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F. van den Akker I. K. Feil C. Roach A. A. Platas E. A. Merritt W. G. Hol 《Protein science : a publication of the Protein Society》1997,6(12):2644-2649
Cholera toxin (CT) produced by Vibrio cholerae and heat-labile enterotoxin (LT-I), produced by enterotoxigenic Escherichia coli, are AB5 heterohexamers with an ADP-ribosylating A subunit and a GM1 receptor binding B pentamer. These toxins are among the most potent mucosal adjuvants known and, hence, are of interest both for the development of anti-diarrheal vaccines against cholera or enterotoxigenic Escherichia coli diarrhea and also for vaccines in general. However, the A subunits of CT and LT-I are known to be relatively temperature sensitive. To improve the thermostability of LT-I an additional disulfide bond was introduced in the A1 subunit by means of the double mutation N40C and G166C. The crystal structure of this double mutant of LT-I has been determined to 2.0 A resolution. The protein structure of the N40C/G166C double mutant is very similar to the native structure except for a few local shifts near the new disulfide bond. The introduction of this additional disulfide bond increases the thermal stability of the A subunit of LT-I by 6 degrees C. The enhancement in thermostability could make this disulfide bond variant of LT-I of considerable interest for the design of enterotoxin-based vaccines. 相似文献
134.
Yoshio Fujii Tomohiko Nomura Hiromi Kanzawa Michio Kameyama Hiroyasu Yamanaka Masahiko Akita Kojun Setsu Keinosuke Okamoto 《Microbiology and immunology》1998,42(10):703-714
We purified the toxin of Aeromonas sobria capable of inducing a positive response in the mouse intestinal loop assay. The purified toxin showed a positive response not only in the loop assay but also in a hemolytic assay. Subsequently, we cloned the toxin gene and demonstrated that the product of this gene possessed both hemolytic and enterotoxic activities. These results showed that the enterotoxin of A. sobria possesses hemolytic activity. Nucleotide sequence determination of the toxin gene and amino acid sequence analysis of the purified toxin revealed that it is synthesized as a precursor composed of 488 amino acid residues, and that the 24 amino-terminal amino acid residues of the precursor is removed in the mature toxin. As antiserum against the purified toxin neutralized the fluid accumulation induced by living cells not only of A. sobria but also of A. hydrophila, this and antigenically related toxin(s) are thought to play an essential role in the induction of diarrhea by these organisms. The toxin-injured Chinese hamster ovary (CHO) cells induced the release of intracellular lactose dehydrogenase (LDH). The release of LDH from CHO cells and the lysis of erythrocytes by the toxin were repressed by the addition of dextran to the reaction solution, indicating that the toxin forms pores in the membranes and that the cells were injured by the osmotic gradient developed due to pore formation. However, the histopathological examination of intestinal cells exposed to the toxin showed that it caused fluid accumulation in the mouse intestinal loop without causing cellular damage. 相似文献
135.
Shi L Miyoshi S Hiura M Tomochika K Shimada T Shinoda S 《Microbiology and immunology》1998,42(12):823-828
A total of 51 clinical strains of Vibrio mimicus were searched for the presence of virulence-associated genes, like ctx, zot or ace genes which locate in "cholera virulence cassette," and the st gene by polymerase chain reaction. Moreover, the pathological potential of each clinical strain was also examined by rabbit ileal loop (RIL). Three strains showed to have the ctx gene, of which only one strain was zot gene-positive. Meanwhile, one other strain was zot+ but ctx-. All of these four strains were found to have the ace gene and to belong to serogroup O115. Nine strains showed to carry the st gene. However, none of these ST-gene-positive strains was indicated to contain the genes located in the "cholera virulence cassette." It is of interest to note that all of the RIL-positive and/or virulence gene-positive strains were restricted to three serogroups, O20, O41 and O115. These results suggest a significant association between O antigens and enterotoxic activities in V. mimicus clinical strains, and clearly demonstrate multifactorial virulence potentials of this human pathogen. 相似文献
136.
Binding protein for Escherichia coli heat-stable enterotoxin II in mouse intestinal membrane 总被引:1,自引:0,他引:1
Abstract The protein binding Escherichia coli heat-stable enterotoxin II (STII) was isolated from cell membranes of mouse intestine. The binding of 125 I-labeled STII to the proteins was inhibited by unlabeled STII, showing that it is specific. Proteins cross-linked with 125 I-STII were purified by column chromatography on hydroxyapatite and TSK gel. Analyses of the purified protein by SDS-polyacrylamide gel electrophorosis and gel filtration showed that the molecular mass was 25 kDa. 相似文献
137.
C. L. Verlinde E. A. Merritt F. Van den Akker H. Kim I. Feil L. F. Delboni S. C. Mande S. Sarfaty P. H. Petra W. G. Hol 《Protein science : a publication of the Protein Society》1994,3(10):1670-1686
The current rapid growth in the number of known 3-dimensional protein structures is producing a database of structures that is increasingly useful as a starting point for the development of new medically relevant molecules such as drugs, therapeutic proteins, and vaccines. This development is beautifully illustrated in the recent book, Protein structure: New approaches to disease and therapy (Perutz, 1992). There is a great and growing promise for the design of molecules for the treatment or prevention of a wide variety of diseases, an endeavor made possible by the insights derived from the structure and function of crucial proteins from pathogenic organisms and from man. We present here 2 illustrations of structure-based drug design. The first is the prospect of developing antitrypanosomal drugs based on crystallographic, ligand-binding, and molecular modeling studies of glycolytic glycosomal enzymes from Trypanosomatidae. These unicellular organisms are responsible for several tropical diseases, including African and American trypanosomiases, as well as various forms of leishmaniasis. Because the target enzymes are also present in the human host, this project is a pioneering study in selective design. The second illustrative case is the prospect of designing anti-cholera drugs based on detailed analysis of the structure of cholera toxin and the closely related Escherichia coli heat-labile enterotoxin. Such potential drugs can be targeted either at inhibiting the toxin's receptor binding site or at blocking the toxin's intracellular catalytic activity. Study of the Vibrio cholerae and E. coli toxins serves at the same time as an example of a general approach to structure-based vaccine design. These toxins exhibit a remarkable ability to stimulate the mucosal immune system, and early results have suggested that this property can be maintained by engineered fusion proteins based on the native toxin structure. The challenge is thus to incorporate selected epitopes from foreign pathogens into the native framework of the toxin such that crucial features of both the epitope and the toxin are maintained. That is, the modified toxin must continue to evoke a strong mucosal immune response, and this response must be directed against an epitope conformation characteristic of the original pathogen. 相似文献
138.
Isolation of a new ssDNA aptamer against staphylococcal enterotoxin B based on CNBr‐activated sepharose‐4B affinity chromatography
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Mojtaba Hedayati Ch Jafar Amani Hamid Sedighian Mohsen Amin Jafar Salimian Raheleh Halabian Abbas Ali Imani Fooladi 《Journal of molecular recognition : JMR》2016,29(9):436-445
Staphylococcus aureus are potent human pathogens possessing arsenal of virulence factors. Staphylococcal food poisoning (SFP) and respiratory infections mediated by staphylococcal enterotoxin B (SEB) are common clinical manifestations. Many diagnostic techniques are based on serological detection and quantification of SEB in different food and clinical samples. Aptamers are known as new therapeutic and detection tools which are available in different ssDNA, dsDNA and protein structures. In this study, we used a new set of ssDNA aptamers against SEB. The methods used included preparation of a dsDNA library using standard SEB protein as the target analyte, affinity chromatography matrix in microfuge tubes, SELEX procedures to isolate specific ssDNA‐aptamer as an affinity ligand, aptamer purification using ethanol precipitation method, affinity binding assay using ELISA, aptamer cloning and specificity test. Among 12 readable sequences, three of them were selected as the most appropriate aptamer because of their affinity and specificity to SEB. This study presents a new set of ssDNA aptamer with favorable selectivity to SEB through 12 rounds of SELEX. Selected aptamers were used to detect SEB in infected serum samples. Results showed that SEB c1 aptamer (2 µg SEB/100 nM aptamer) had favorable specificity to SEB (kd = 2.3 × 10?11). In conclusion, aptamers can be considered as useful tools for detecting and evaluating SEB. The results showed that affinity chromatography was an affordable assay with acceptable accuracy to isolate sensitive and selective novel aptamers. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
139.
140.
Cloxacillin control of experimental arthritis induced by SEC+ Staphylococcus aureus is associated with downmodulation of local and systemic cytokines
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Priscila Maria Colavite Larissa Lumi Watanabe Ishikawa Sofia Fernanda Gonçalves Zorzella‐Pezavento Larissa Ragozo Cardoso de Oliveira Thaís Graziela Donegá França Larissa Camargo da Rosa Fernanda Chiuso‐Minicucci Andreia Espíndola Vieira Carolina Fávaro Francisconi Maria de Lourdes Ribeiro de Souza da Cunha Gustavo Pompermaier Garlet Alexandrina Sartori 《Cellular microbiology》2016,18(7):998-1008