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排序方式: 共有553条查询结果,搜索用时 109 毫秒
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Borrello MG Mercalli E Perego C Degl'Innocenti D Ghizzoni S Arighi E Eroini B Rizzetti MG Pierotti MA 《Biochemical and biophysical research communications》2002,296(3):515-522
The receptor tyrosine kinase RET, with a known role in embryonic development and in human pathologies, is alternatively spliced to yield at least two functional isoforms, which differ only in their carboxyl terminal. Enigma protein is a member of the PDZ-LIM family and is known to interact with the short isoform of RET/PTC2, a chimeric oncoprotein isolated from papillary thyroid carcinoma. Here, we show that Enigma also interacts in intact cells with the short isoform of RET-wt and of its pathologic mutants associated to MEN2 syndromes, RET-C634R and RET-M918T. In contrast, Enigma binds all the corresponding RET long isoforms very poorly and colocalizes with short but not long RET/PTC2 isoforms. The RET docking tyrosine for Enigma is the last but one before the divergence between the two isoforms and we demonstrated that short-isoform-specific amino acid residues +2 to +4 to this tyrosine are required for the interaction of RET/PTC2 with Enigma. 相似文献
33.
Zanotto C Elli V Basavecchia V Brivio A Paganini M Pinna D Vicenzi E De Giuli Morghen C Radaelli A 《FEMS immunology and medical microbiology》2003,35(1):59-65
Two different prime-boost immunization protocols were tested in rabbits and their immune response was evaluated and compared with the final aim of defining a vaccine strategy that might be able to protect non-human primates from infection with the pathogenic simian/human immunodeficiency virus, SHIV(89.6P). The two regimens were based on three priming immunizations with either an expression plasmid plus a fowlpox (FP) recombinant vector or with two FP recombinant vectors, each one expressing either the SIV(mac239) gag/pol or the HIV-1env(89.6P) genes. In both protocols, priming immunizations were followed by two boosts with SHIV-mimicking virus-like particles (VLP). A complete SHIV-specific response was observed in all animals. Interestingly, the DNA vaccine was three to 10 times more efficient than the FP recombinant in inducing an anti-gag humoral response. Real-time PCR confirmed the memory effect on T-cell subsets secreting interleukin-4 and interferon-gamma, as a consequence of stimulation of both arms of the immune system. Although both protocols were almost equally effective in eliciting homologous neutralizing antibodies and highlighted the efficacy of VLP administration for boosting, protocol A seemed to be more effective in promoting a balanced T-cell memory immune response and appears more promising for vaccine purposes. 相似文献
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Angélica F. Arcanjo Isabel F. LaRocque-de-Freitas Juliana Dutra B. Rocha Daniel Zamith Ana Caroline Costa-da-Silva Marise Pinheiro Nunes Fabio P. Mesquita-Santos Alexandre Morrot Alessandra A. Filardy Mario Mariano Christianne Bandeira-Melo George A. DosReis Debora Decote-Ricardo Célio Geraldo Freire-de-Lima 《PloS one》2015,10(5)
B-1 cells can be differentiated from B-2 cells because they are predominantly located in the peritoneal and pleural cavities and have distinct phenotypic patterns and activation properties. A mononuclear phagocyte derived from B-1 cells (B-1CDP) has been described. As the B-1CDP cells migrate to inflammatory/infectious sites and exhibit phagocytic capacity, the microbicidal ability of these cells was investigated using the Leishmania major infection model in vitro. The data obtained in this study demonstrate that B-1CDP cells are more susceptible to infection than peritoneal macrophages, since B-1CDP cells have a higher number of intracellular amastigotes forms and consequently release a larger number of promastigotes. Exacerbated infection by L. major required lipid bodies/PGE2 and IL-10 by B-1CDP cells. Both infection and the production of IL-10 were decreased when PGE2 production was blocked by NSAIDs. The involvement of IL-10 in this mechanism was confirmed, since B-1CDP cells from IL-10 KO mice are more competent to control L. major infection than cells from wild type mice. These findings further characterize the B-1CDP cells as an important mononuclear phagocyte that plays a previously unrecognized role in host responses to L. major infection, most likely via PGE2-driven production of IL-10. 相似文献
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Targeting Ergosterol Biosynthesis in Leishmania donovani: Essentiality of Sterol 14alpha-demethylase
Laura-Isobel McCall Amale El Aroussi Jun Yong Choi Debora F. Vieira Geraldine De Muylder Jonathan B. Johnston Steven Chen Danielle Kellar Jair L. Siqueira-Neto William R. Roush Larissa M. Podust James H. McKerrow 《PLoS neglected tropical diseases》2015,9(3)
Leishmania protozoan parasites (Trypanosomatidae family) are the causative agents of cutaneous, mucocutaneous and visceral leishmaniasis worldwide. While these diseases are associated with significant morbidity and mortality, there are few adequate treatments available. Sterol 14alpha-demethylase (CYP51) in the parasite sterol biosynthesis pathway has been the focus of considerable interest as a novel drug target in Leishmania. However, its essentiality in Leishmania donovani has yet to be determined. Here, we use a dual biological and pharmacological approach to demonstrate that CYP51 is indispensable in L. donovani. We show via a facilitated knockout approach that chromosomal CYP51 genes can only be knocked out in the presence of episomal complementation and that this episome cannot be lost from the parasite even under negative selection. In addition, we treated wild-type L. donovani and CYP51-deficient strains with 4-aminopyridyl-based inhibitors designed specifically for Trypanosoma cruzi CYP51. While potency was lower than in T. cruzi, these inhibitors had increased efficacy in parasites lacking a CYP51 allele compared to complemented parasites, indicating inhibition of parasite growth via a CYP51-specific mechanism and confirming essentiality of CYP51 in L. donovani. Overall, these results provide support for further development of CYP51 inhibitors for the treatment of visceral leishmaniasis. 相似文献
39.
Francine P. Favaro Lucas Alvizi Roseli M. Zechi-Ceide Debora Bertola Temis M. Felix Josiane de Souza Salmo Raskin Stephen R.F. Twigg Andrea M.J. Weiner Pablo Armas Ezequiel Margarit Nora B. Calcaterra Gregers R. Andersen Simon J. McGowan Andrew O.M. Wilkie Antonio Richieri-Costa Maria L.G. de Almeida Maria Rita Passos-Bueno 《American journal of human genetics》2014
40.
Immunostaining for nucleophosmin in bone marrow trephine biopsy specimens in acute myeloid leukemias