全文获取类型
收费全文 | 372篇 |
免费 | 30篇 |
出版年
2023年 | 1篇 |
2022年 | 7篇 |
2021年 | 15篇 |
2020年 | 5篇 |
2019年 | 4篇 |
2018年 | 16篇 |
2017年 | 10篇 |
2016年 | 9篇 |
2015年 | 19篇 |
2014年 | 17篇 |
2013年 | 27篇 |
2012年 | 34篇 |
2011年 | 38篇 |
2010年 | 20篇 |
2009年 | 14篇 |
2008年 | 30篇 |
2007年 | 25篇 |
2006年 | 16篇 |
2005年 | 29篇 |
2004年 | 23篇 |
2003年 | 12篇 |
2002年 | 16篇 |
2001年 | 1篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1997年 | 3篇 |
1996年 | 1篇 |
1994年 | 1篇 |
1993年 | 3篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1982年 | 1篇 |
排序方式: 共有402条查询结果,搜索用时 203 毫秒
61.
Camila Marques-da-Silva Mariana M. Chaves Maria Luiza Thorstenberg Vanessa R. Figliuolo Flávia S. Vieira Suzana P. Chaves José Roberto Meyer-Fernandes Bartira Rossi-Bergmann Luiz Eduardo Baggio Savio Robson Coutinho-Silva 《Purinergic signalling》2018,14(2):201-211
Leishmania amazonensis is the etiologic agent of cutaneous leishmaniasis, an immune-driven disease causing a range of clinical symptoms. Infections caused by L. amazonensis suppress the activation and function of immune cells, including macrophages, dendritic cells, and CD4+ T cells. In this study, we analyzed the course of infection as well as the leishmanicidal effect of intralesional UTP treatment in L. amazonensis-infected BALB/c mice. We found that UTP treatment reduced the parasitic load in both footpad and lymph node sites of infection. UTP also boosted Th1 immune responses, increasing CD4+ T cell recruitment and production of IFN-γ, IL-1β, IL-12, and TNF-α. In addition, the role of UTP during innate immune response against L. amazonensis was evaluated using the air pouch model. We observed that UTP augmented neutrophil chemoattraction and activated microbicidal mechanisms, including ROS production. In conclusion, our data suggested an important role for this physiological nucleotide in controlling L. amazonensis infection, and its possible use as a therapeutic agent for shifting immune responses to Th1 and increasing host resistance against L. amazonensis infection. 相似文献
62.
63.
Elroy J. Pereira Suzana Fonseca Ram M. Meena Nagappa Ramaiah 《Indian journal of microbiology》2017,57(4):400-408
Marine bacteria possess a wide variety of bioremediation potential which is beneficial environmentally and economically. In this study, bacterial isolates from marine waters were screened for tolerance and growth in high concentrations of chromate (Cr6+). Two isolates, capable of tolerating Cr6+ concentrations 300 µg mL?1 or higher, and found to completely reduce 20 µg mL?1 Cr6+ were grown in Cr6+ (50 and 100 mg kg?1) spiked garden soil. Notably, both facilitated normal germination and growth of mung (Vigna radiata) seeds, which could hardly germinate in Cr6+ spiked garden soil without either of these bacteria. In fact, large percent of mung seeds failed to sprout in the Cr6+ spiked garden soil and could not grow any further. Apparently, chromate detoxification by marine bacterial isolates and the ability of mung plants to deal with the reduced form appear to work complementarily. This study provides an insight into marine bacterial abilities with respect to chromium and potential applications in promoting growth of leguminous plants-similar to mung in particular-in Cr6+ contaminated soil. 相似文献
64.
The Mre11 complex (Mre11, Rad50, and Nbs1) and Chk2 have been implicated in the DNA-damage response, an inducible process required for the suppression of malignancy. The Mre11 complex is predominantly required for repair and checkpoint activation in S phase, whereas Chk2 governs apoptosis. We examined the relationship between the Mre11 complex and Chk2 in the DNA-damage response via the establishment of Nbs1(DeltaB/DeltaB) Chk2(-/-) and Mre11(ATLD1/ATLD1) Chk2(-/-) mice. Chk2 deficiency did not modify the checkpoint defects or chromosomal instability of Mre11 complex mutants; however, the double-mutant mice exhibited synergistic defects in DNA-damage-induced p53 regulation and apoptosis. Nbs1(DeltaB/DeltaB) Chk2(-/-) and Mre11(ATLD1/ATLD1) Chk2(-/-) mice were also predisposed to tumors. In contrast, DNA-PKcs-deficient mice, in which G1-specific chromosome breaks are present, did not exhibit synergy with Chk2(-/-) mutants. These data suggest that Chk2 suppresses the oncogenic potential of DNA damage arising during S and G2 phases of the cell cycle. 相似文献
65.
Salcedo SP Marchesini MI Lelouard H Fugier E Jolly G Balor S Muller A Lapaque N Demaria O Alexopoulou L Comerci DJ Ugalde RA Pierre P Gorvel JP 《PLoS pathogens》2008,4(2):e21
Brucella is an intracellular pathogen able to persist for long periods of time within the host and establish a chronic disease. We show that soon after Brucella inoculation in intestinal loops, dendritic cells from ileal Peyer's patches become infected and constitute a cell target for this pathogen. In vitro, we found that Brucella replicates within dendritic cells and hinders their functional activation. In addition, we identified a new Brucella protein Btp1, which down-modulates maturation of infected dendritic cells by interfering with the TLR2 signaling pathway. These results show that intracellular Brucella is able to control dendritic cell function, which may have important consequences in the development of chronic brucellosis. 相似文献
66.
Marina Jendrach Suzana Gispert Filomena Ricciardi Michael Klinkenberg Rudolf Schemm Georg Auburger 《Journal of bioenergetics and biomembranes》2009,41(6):481-486
Mitochondrial dysfunction is well documented in presymptomatic brain tissue with Parkinson’s disease (PD). Identification
of the autosomal recessive variant PARK6 caused by loss-of-function mutations in the mitochondrial kinase PINK1 provides an
opportunity to dissect pathogenesis. Although PARK6 shows clinical differences to PD, the induction of alpha-synuclein “Lewy”
pathology by PINK1-deficiency proves that mitochondrial pathomechanisms are relevant for old-age PD. Mitochondrial dysfunction
is induced by PINK1 deficiency even in peripheral tissues unaffected by disease, consistent with the ubiquitous expression
of PINK1. It remains unclear whether this dysfunction is due to PINK1-mediated phosphorylation of proteins inside or outside
mitochondria. Although PINK1 deficiency affects the mitochondrial fission/fusion balance, cell stress is required in mammals
to alter mitochondrial dynamics and provoke apoptosis. Clearance of damaged mitochondria depends on pathways including PINK1
and Parkin and is critical for postmitotic neurons with high energy demand and cumulative stress, providing a mechanistic
concept for the tissue specificity of disease. 相似文献
67.
Raquel Vilela Patricia S. Rosa Andra F.F. Belone John W. Taylor Suzana M. Dirio Leonel Mendoza 《Mycological Research》2009,113(8):851-857
Lacazia loboi is a geographically restricted, uncultivated fungal pathogen of humans and dolphins. Previous investigations using 18S small unit rDNA, chitin synthase 2 and gp43 DNA sequences positioned L. loboi as a close relative of Paracoccidioides brasiliensis. However, given the few individuals of L. loboi studied and the high degree of genetic variation observed in P. brasiliensis, the existence of L. loboi as an independent species has been questioned. To investigate the phylogenetic position of this species, we conducted a phylogenetic analysis using 20 L. loboi collections (L. loboi was obtained from proven cases of lacaziosis and 14 collections were maintained in mice, the others were analyzed from DNA taken directly from infected human tissue.). L. loboi DNA sequence was compared to that from 17 P. brasiliensis strains that represented the known variation in this species, and outgroup taxa in the Onygenales (Ajellomyces and Coccidioides species). Our analyses used DNA sequence from ITS rRNA, and partial coding sequences of chitin synthase 4, ADP-ribosylation factor, and gp43. Nucleotide variation among strains of L. loboi was minor but numerous nucleotide mismatches and multiple gaps were found for these gene regions among members in the Ajellomycetaceae, including P. brasiliensis. Phylogenies inferred using neighbor-joining, maximum parsimony and Bayesian analyses showed no significant conflict and depicted L. loboi as a well-supported, monophyletic group that was sister to the Paracoccidioides clade. These results argue for maintaining L. loboi as a taxon independent from Paracoccidioides within the Ajellomycetaceae. 相似文献
68.
Junjun Wu Neal Green Rajeev Hotchandani Yonghan Hu Jeffrey Condon Adrian Huang Neelu Kaila Huan-Qiu Li Satenig Guler Wei Li Steve Y. Tam Qin Wang Jeffrey Pelker Suzana Marusic Sang Hsu J. Perry Hall Jean-Baptiste Telliez Junqing Cui Lih-Ling Lin 《Bioorganic & medicinal chemistry letters》2009,19(13):3485-3488
Tpl2 (cot/MAP3K8) is an upstream kinase of MEK in the ERK pathway. It plays an important role in Tumor Necrosis Factor-α (TNF-α) production and signaling. We have discovered that 8-halo-4-(3-chloro-4-fluoro-phenylamino)-6-[(1H-[1,2,3]triazol-4-ylmethyl)-amino]-quinoline-3-carbonitriles (4) are potent inhibitors of this enzyme. In order to improve the inhibition of TNF-α production in LPS-stimulated human blood, a series of analogs with a variety of substitutions around the triazole moiety were studied. We found that a cyclic amine group appended to the triazole ring could considerably enhance potency, aqueous solubility, and cell membrane permeability. Optimization of these cyclic amine groups led to the identification of 8-chloro-4-(3-chloro-4-fluorophenylamino)-6-((1-(1-ethylpiperidin-4-yl)-1H-1,2,3-triazol-4-yl)methylamino)quinoline-3-carbonitrile (34). In a LPS-stimulated rat inflammation model, compound 34 showed good efficacy in inhibiting TNF-α production. 相似文献
69.
Suzana Passos Chaves Eduardo Caio Torres-Santos Camila Marques Vanessa Ribeiro Figliuolo Pedro Muanis Persechini Robson Coutinho-Silva Bartira Rossi-Bergmann 《Microbes and infection / Institut Pasteur》2009,11(10-11):842-849
The purinergic P2X7 receptor is a membrane protein of leucocytes involved in the clearance of intracellular bacteria such as Chlamydia and Mycobacterium. In this work, we investigated the role and modulation of macrophage P2X7R in intracellular infection with the protozoan parasite Leishmania amazonensis. Upon infection, isolated murine macrophages displayed enhanced expression of P2X7R and were significantly more responsive to extracellular ATP (ATPe)-induced pore opening, as demonstrated by the increased uptake of Lucifer Yellow. This was extended to the in vivo situation, where cells from established cutaneous lesions were more sensitive to ATPe than cells from uninfected mice. ATP treatment of infected macrophages inhibited parasite growth, and this was prevented by pre-treatment with oxidized ATP, a selective antagonist of P2X7R. Parasite killing was unlikely due to induction of nitric oxide production or cytolysis of infected macrophage, as those functions were unaltered with parasite-effective ATPe concentrations. A direct drug effect is also unlike, as ATPe enhanced axenic parasite growth. We found that leishmanial infection rendered wild-type but not P2X7R-deficient macrophages more prone to ATP-induced apoptosis. These results show that macrophage infection with L. amazonensis leads to enhanced expression of functional P2X7R, that upon ligation with ATPe helps in the elimination of the parasites by an as yet unclear mechanism possibly involving host cell apoptosis. 相似文献
70.