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51.
Wang XF Cohen WM Castelli FA Almunia C Lethé B Pouvelle-Moratille S Munier G Charron D Ménez A Zarour HM van der Bruggen P Busson M Maillère B 《Cancer immunology, immunotherapy : CII》2007,56(6):807-818
Because of the high frequency of HLA-DP4 in the Caucasian population, we have selectively delineated HLA-DP4 restricted T
cell epitopes in the MAGE-A tumor antigens. We identified 12 good binders to HLA-DP4 and investigated the capacity of the
seven best binders to induce in vitro specific CD4+ T cell lines from HLA-DP4 healthy donors. We found that the MAGE-A1 90–104
peptide exhibited a high and constant frequency of CD4+ T cell precursors in all the six tested donors. The MAGE-A1 268–282
peptide was found immunogenic in only two donors but with a high precursor frequency. The MAGE-A12 127–141 peptide was T cell
stimulating in six different donors and induced fewer T cell lines. The peptide-specific T cell lines were stimulated by DC
loaded with the lysates of cells transfected with MAGE-A1 or MAGE-A12, or loaded with the recombinant protein. We also show
that the immunoreactivity of CD4+ T cell epitopes restricted to the same HLA II molecule may vary from one individual to another,
as a result of inter-individual variations in the CD4+ T cell repertoire. 相似文献
52.
Paolo Puccetti Francesca Fallarino Antoine Italiano Isabelle Soubeyran Gaetan MacGrogan Marc Debled Valerie Velasco Dominique Bodet Sandrine Eimer Marc Veldhoen Georges C. Prendergast Michael Platten Alban Bessede Gilles J. Guillemin 《PloS one》2015,10(4)
Tumor immune escape mechanisms are being regarded as suitable targets for tumor therapy. Among these, tryptophan catabolism plays a central role in creating an immunosuppressive environment, leading to tolerance to potentially immunogenic tumor antigens. Tryptophan catabolism is initiated by either indoleamine 2,3-dioxygenase (IDO-1/-2) or tryptophan 2,3-dioxygenase 2 (TDO2), resulting in biostatic tryptophan starvation and l-kynurenine production, which participates in shaping the dynamic relationship of the host’s immune system with tumor cells. Current immunotherapy strategies include blockade of IDO-1/-2 or TDO2, to restore efficient antitumor responses. Patients who might benefit from this approach are currently identified based on expression analyses of IDO-1/-2 or TDO2 in tumor tissue and/or enzymatic activity assessed by kynurenine/tryptophan ratios in the serum. We developed a monoclonal antibody targeting l-kynurenine as an in situ biomarker of IDO-1/-2 or TDO2 activity. Using Tissue Micro Array technology and immunostaining, colorectal and breast cancer patients were phenotyped based on l-kynurenine production. In colorectal cancer l-kynurenine was not unequivocally associated with IDO-1 expression, suggesting that the mere expression of tryptophan catabolic enzymes is not sufficiently informative for optimal immunotherapy. 相似文献
53.
54.
Patrick M. Lelliott Brendan J. McMorran Simon J. Foote Gaetan Burgio 《Journal of visualized experiments : JoVE》2015,(98)
During blood stage infection, malaria parasites invade, mature, and replicate within red blood cells (RBCs). This results in a regular growth cycle and an exponential increase in the proportion of malaria infected RBCs, known as parasitemia. We describe a flow cytometry based protocol which utilizes a combination of the DNA dye Hoechst, and the mitochondrial membrane potential dye, JC-1, to identify RBCs which contain parasites and therefore the parasitemia, of in vivo blood samples from Plasmodium chabaudi adami DS infected mice. Using this approach, in combination with fluorescently conjugated antibodies, parasitized RBCs can be distinguished from leukocytes, RBC progenitors, and RBCs containing Howell-Jolly bodies (HJ-RBCs), with a limit of detection of 0.007% parasitemia. Additionally, we outline a method for the comparative assessment of merozoite invasion into two different RBC populations. In this assay RBCs, labeled with two distinct compounds identifiable by flow cytometry, are transfused into infected mice. The relative rate of invasion into the two populations can then be assessed by flow cytometry based on the proportion of parasitized RBCs in each population over time. This combined approach allows the accurate measurement of both parasitemia and merozoite invasion in an in vivo model of malaria infection. 相似文献
55.
Erfan Aref-Eshghi Jennifer Kerkhof Victor P. Pedro Groupe DI France Mouna Barat-Houari Nathalie Ruiz-Pallares Jean-Christophe Andrau Didier Lacombe Julien Van-Gils Patricia Fergelot Christéle Dubourg Valerie Cormier-Daire Sophie Rondeau François Lecoquierre Pascale Saugier-Veber Gaël Nicolas Gaetan Lesca Nicolas Chatron Bekim Sadikovic 《American journal of human genetics》2021,108(6):1161-1163
56.
Emeline Fabre Gilles Joucla Claire Moulis Stephane Emond Gaetan Richard Gabrielle Potocki-Veronese 《Biocatalysis and Biotransformation》2013,31(1-2):137-145
Glucansucrases from family 70 of glycoside-hydrolases catalyse the synthesis of α-glucans with various types of osidic linkages from sucrose. Among these enzymes, alternansucrase (ASR) and dextransucrase E (DSR-E) catalyse the formation of unusual α-glucans. ASR catalyses the synthesis of linear glucan with α-1,3 and α-1,6 alternating linkages and DSR-E synthesizes a glucan containing α-1,6 linkages in the linear chain and α-1,2 branches. The sequence analysis of these enzymes enabled the identification of structural elements suspected to be involved in the enzyme specificities. Biochemical characterization of ASR and DSR-E variants obtained from gene truncations or site-directed mutagenesis experiments showed that the specificity of these enzymes to form different types of osidic linkage is controlled by two different approaches. For ASR, the double specificity is controlled by only one catalytic domain where important amino acids involved in the enzyme specificity have been identified. In the case of DSR-E, the double specificity is controlled by two different catalytic domains both belonging to family 70, each domain being specific of one type of linkage. 相似文献
57.
Gavazzi G Banfi B Deffert C Fiette L Schappi M Herrmann F Krause KH 《FEBS letters》2006,580(2):497-504
To understand the role of the superoxide-generating NADPH oxidase NOX1 in the vascular system, we have generated NOX1-deficient mice. NOX1-deficient mice had a moderately decreased basal blood pressure. In response to angiotensin II they showed an almost complete loss of the sustained blood pressure response, while the initial increase was conserved. NOX1-deficient mice showed a marked reduction in aortic media hypertrophy. Angiotensin II-induced smooth muscle cell proliferation was conserved, but there was a marked decrease in extracellular matrix accumulation. Our results establish a role for NOX1 in blood pressure regulation and vascular angiotensin II response. 相似文献
58.
Houthoofd W Willems M Jacobsen K Coomans A Borgonie G 《The International journal of developmental biology》2008,52(7):963-967
One of the unique features of the model organism Caenorhabditis elegans is its invariant development, where a stereotyped cell lineage generates a fixed number of cells with a fixed cell type. It remains unclear how embryonic development evolved within the nematodes to give rise to the complex, invariant cell lineage of C. elegans. Therefore, we determined the embryonic cell lineage of the nematode, Rhabditophanes sp. (family Alloionematidae) and made detailed cell-by-cell comparison with the known cell lineages of C. elegans, Pellioditis marina and Halicephalobus gingivalis. This gave us a unique data set of four embryonic cell lineages, which allowed a detailed comparison between these cell lineages at the level of each individual cell. This lineage comparison revealed a similar complex polyclonal fate distribution in all four nematode species (85% of the cells have the same fate). It is striking that there is a conservation of a 'C. elegans' like polyclonal cell lineage with strong left-right asymmetry. We propose that an early symmetry-breaking event in nematodes of clade IV-V is a major developmental constraint which shapes their asymmetric cell lineage. 相似文献
59.
Wang XF Kerzerho J Adotevi O Nuyttens H Badoual C Munier G Oudard S Tu S Tartour E Maillère B 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(1):431-439
Because of the wide distribution of the survivin Ag in a variety of tumors, we have investigated the survivin-specific CD4+ T cell response in healthy donors and cancer patients. Screening of the entire sequence of survivin for HLA class II binding led to the identification of seven HLA-DR promiscuous peptides, including four HLA-DP4 peptides. All of the peptides were able to prime in vitro CD4+ T cells of eight different healthy donors. The peptide-specific T cell lines were stimulated by dendritic cells loaded with the recombinant protein or with the lysates of tumor cells. The high frequency of responders (i.e., immunoprevalence) was provided by a wide reactivity of multiple peptides. Six peptides were T cell stimulating in at least half of the donors and were close to CD8+ T cell epitopes. HLA-DR molecules were more frequently involved in T cell stimulation than were HLA-DP4 molecules, and hence immunoprevalence relies mainly on HLA-DR promiscuity in the survivin Ag. In two cancer patients a spontaneous CD4+ T cell response specific for one of these peptides was also observed. Based on these observations, the tumor-shared survivin does not appear to be the target of immune tolerance in healthy donors and cancer patients and is a relevant candidate for cancer vaccine. 相似文献
60.
A multiple-imputation Metropolis version of the EM algorithm 总被引:2,自引:0,他引:2