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排序方式: 共有95条查询结果,搜索用时 15 毫秒
71.
Petretski JH Kanashiro MM Rodrigues FR Alves EW Machado OL Kipnis TL 《Biochemical and biophysical research communications》2000,276(1):29-34
Viperine and crotaline snake venoms contain one or more hemorrhagic metalloproteases called hemorrhagins. The most potent hemorrhagins belong to the P-III class and have, in addition to the protease domain, disintegrin-like and cysteine-rich domains. Although proteolytic degradation of vascular endothelium basement membrane has been established to be the main factor responsible for hemorrhage, several studies reveal other factors that actually do facilitate this process. Recent evidence has shown that the nonprotease domains of the P-III class hemorrhagins are able to inhibit the platelet aggregation by blocking essential procoagulant integrins on platelets. In this study we report the identification of a hemorrhagin from Bothrops atrox venom. This enzyme, a P-III class metalloprotease, undergoes an apparent spontaneous degradation, releasing a proteic fragment containing the disintegrin-like/cysteine-rich domains. This fragment shows the capability to induce an edematogenic process, suggesting the existence of a still unknown nonenzymatic mechanism of vascular permeability increase. 相似文献
72.
Mice lacking bioactive IL-12 can generate protective, antigen-specific cellular responses to mycobacterial infection only if the IL-12 p40 subunit is present. 总被引:27,自引:0,他引:27
Andrea M Cooper Andre Kipnis Joanne Turner Jeanne Magram Jessica Ferrante Ian M Orme 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(3):1322-1327
Recent evidence suggests that absence of the IL-12p40 subunit is more detrimental to the generation of protective responses than is the absence of the p35 subunit. To determine whether this is the case in tuberculosis, both p35 and p40 knockout mice were infected with Mycobacterium tuberculosis. Mice lacking the p40 subunit were highly susceptible to increased bacterial growth, exhibited reduced production of IFN-gamma, and had increased mortality. In contrast, mice lacking the p35 subunit exhibited a moderate ability to control bacterial growth, were able to generate Ag-specific IFN-gamma responses, and survived infection longer. The superior Ag-specific responses of the p35 gene-disrupted mice, when compared with the p40 gene-disrupted mice, suggest that the p40 subunit may act other than as a component of IL-12. A candidate molecule capable of driving the protective responses in the p35 gene-disrupted mice is the novel cytokine IL-23. This cytokine is composed of the IL-12 p40 subunit and a p19 subunit. In support of a role for this cytokine in protective responses to M. tuberculosis, we determined that the p19 subunit is induced in the lungs of infected mice. 相似文献
73.
Rogerio Coutinho das Neves Monalisa Martins Trentini Juliana de Castro e Silva Karina Smidt Simon Anamelia Lorenzetti Bocca Luciano Paulino Silva Marcia Renata Mortari Andre Kipnis Ana Paula Junqueira-Kipnis 《PloS one》2016,11(3)
Mycobacterium abscessus subsp. massiliense, a rapidly growing mycobacteria (RGM) that is becoming increasingly important among human infectious diseases, is virulent and pathogenic and presents intrinsic resistance to several antimicrobial drugs that might hamper their elimination. Therefore, the identification of new drugs to improve the current treatment or lower the risk of inducing resistance is urgently needed. Wasp venom primarily comprises peptides that are responsible for most of the biological activities in this poison. Here, a novel peptide Polydim-I, from Polybia dimorpha Neotropical wasp, was explored as an antimycobacterial agent. Polydim-I provoked cell wall disruption and exhibited non-cytotoxicity towards mammalian cells. Polydim-I treatment of macrophages infected with different M. abscessus subsp. massiliense strains reduced 40 to 50% of the bacterial load. Additionally, the Polydim-I treatment of highly susceptible mice intravenously infected with M. abscessus subsp. massiliense induced 0.8 to 1 log reduction of the bacterial load in the lungs, spleen, and liver. In conclusion, this is the first study to show the therapeutic potential of a peptide derived from wasp venom in treating mycobacteria infections. Polydim-I acts on the M. abscessus subsp. massiliense cell wall and reduce 40–90% of the bacterial load both in vitro and in vivo. The presented results encourage further studies on the use of Polydim-I as one of the components for M. abscessus subsp. massiliense treatment. 相似文献
74.
A new colchicine binding assay for tubulin 总被引:11,自引:0,他引:11
A simple and sensitive procedure is described for assaying tubulin, the subunit protein of microtubules. Tubulin is equilibrated with [3H]colchicine after which the remaining free colchicine is removed by adsorption to activated charcoal. Values for the amount of tubulin in various rat tissues have been determined by both the charcoal method and by gel filtration on Sephadex G-100, and in all cases the values determined by the two methods correspond closely. 相似文献
75.
76.
Justin Rustenhoven Antoine Drieu Tornike Mamuladze Kalil Alves de Lima Taitea Dykstra Morgan Wall Zachary Papadopoulos Mitsuhiro Kanamori Andrea Francesca Salvador Wendy Baker Mackenzie Lemieux Sandro Da Mesquita Andrea Cugurra James Fitzpatrick Sanja Sviben Ross Kossina Peter Bayguinov Reid R. Townsend Jonathan Kipnis 《Cell》2021,184(4):1000-1016.e27
77.
A new assay for adenosine 3',5'-cyclic monophosphate in tissue 总被引:4,自引:0,他引:4
78.
Lu Z Elliott MR Chen Y Walsh JT Klibanov AL Ravichandran KS Kipnis J 《Nature cell biology》2011,13(9):1076-1083
Whereas thousands of new neurons are generated daily during adult life, only a fraction of them survive and become part of neural circuits; the rest die, and their corpses are presumably cleared by resident phagocytes. How the dying neurons are removed and how such clearance influences neurogenesis are not well understood. Here, we identify an unexpected phagocytic role for the doublecortin (DCX)-positive neuronal progenitor cells during adult neurogenesis. Our in vivo and ex vivo studies demonstrate that DCX(+) cells comprise a significant phagocytic population within the neurogenic zones. Intracellular engulfment protein ELMO1, which promotes Rac activation downstream of phagocytic receptors, was required for phagocytosis by DCX(+) cells. Disruption of engulfment in vivo genetically (in Elmo1-null mice) or pharmacologically (in wild-type mice) led to reduced uptake by DCX(+) cells, accumulation of apoptotic nuclei in the neurogenic niches and impaired neurogenesis. Collectively, these findings indicate a paradigm wherein DCX(+) neuronal precursors also serve as phagocytes, and that their phagocytic activity critically contributes to neurogenesis in the adult brain. 相似文献
79.
Regulatory CD4(+)CD25(+)Foxp3(+) T cells (Tregs) have been the focus of significant attention for their role in controlling immune responses. Although knowledge of Treg biology has burgeoned, wide gaps remain in our understanding of Treg function under both normal and pathological conditions. Pioneering studies demonstrated roles for Tregs in cancer and autoimmune diseases, including experimental autoimmune encephalitis, and this knowledge is often applied to other pathologies including neurodegenerative conditions. However, differences between immunity in neurodegeneration and in malignancy or autoimmunity are often neglected. Thus, Treg manipulations in central nervous system (CNS) neurodegenerative conditions often yield unexpected outcomes. In this piece, we explore how the immunology of neurodegeneration differs from that of cancer and autoimmunity and how these differences create confusion about the role of Tregs in neurodegenerative conditions. 相似文献
80.
Alves SL Metzker FS Araújo-Filho JA Junqueira-Kipnis AP Kipnis A 《Memórias do Instituto Oswaldo Cruz》2011,106(6):655-661
Drug resistance is one of the major concerns regarding tuberculosis (TB) infection worldwide because it hampers control of the disease. Understanding the underlying mechanisms responsible for drug resistance development is of the highest importance. To investigate clinical data from drug-resistant TB patients at the Tropical Diseases Hospital, Goiás (GO), Brazil and to evaluate the molecular basis of rifampin (R) and isoniazid (H) resistance in Mycobacterium tuberculosis. Drug susceptibility testing was performed on 124 isolates from 100 patients and 24 isolates displayed resistance to R and/or H. Molecular analysis of drug resistance was performed by partial sequencing of the rpoB and katGgenes and analysis of the inhA promoter region. Similarity analysis of isolates was performed by 15 loci mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing. The molecular basis of drug resistance among the 24 isolates from 16 patients was confirmed in 18 isolates. Different susceptibility profiles among the isolates from the same individual were observed in five patients; using MIRU-VNTR, we have shown that those isolates were not genetically identical, with differences in one to three loci within the 15 analysed loci. Drug-resistant TB in GO is caused by M. tuberculosis strains with mutations in previously described sites of known genes and some patients harbour a mixed phenotype infection as a consequence of a single infective event; however, further and broader investigations are needed to support our findings. 相似文献