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71.
Solis M Nakhaei P Jalalirad M Lacoste J Douville R Arguello M Zhao T Laughrea M Wainberg MA Hiscott J 《Journal of virology》2011,85(3):1224-1236
The rapid induction of type I interferon (IFN) is essential for establishing innate antiviral responses. During infection, cytoplasmic viral RNA is sensed by two DExD/H box RNA helicases, RIG-I and MDA5, ultimately driving IFN production. Here, we demonstrate that purified genomic RNA from HIV-1 induces a RIG-I-dependent type I IFN response. Both the dimeric and monomeric forms of HIV-1 were sensed by RIG-I, but not MDA5, with monomeric RNA, usually found in defective HIV-1 particles, acting as a better inducer of IFN than dimeric RNA. However, despite the presence of HIV-1 RNA in the de novo infection of monocyte-derived macrophages, HIV-1 replication did not lead to a substantial induction of IFN signaling. We demonstrate the existence of an evasion mechanism based on the inhibition of the RIG-I sensor through the action of the HIV-1 protease (PR). Indeed, the ectopic expression of PR resulted in the inhibition of IFN regulatory factor 3 (IRF-3) phosphorylation and decreased expression of IFN and interferon-stimulated genes. A downregulation of cytoplasmic RIG-I levels occurred in cells undergoing a single-cycle infection with wild-type provirus BH10 but not in cells transfected with a protease-deficient provirus, BH10-PR(-). Cellular fractionation and confocal microscopy studies revealed that RIG-I translocated from the cytosol to an insoluble fraction during the de novo HIV-1 infection of monocyte-derived macrophages, in the presence of PR. The loss of cytoplasmic RIG-I was prevented by the lysosomal inhibitor E64, suggesting that PR targets RIG-I to the lysosomes. This study reveals a novel PR-dependent mechanism employed by HIV-1 to counteract the early IFN response to viral RNA in infected cells. 相似文献
72.
David J. Mendoza-Aguayo Héctor M. Poggi-Varaldo Jaime García-Mena Ana C. Ramos-Valdivia Luis M. Salgado Mayra de la Torre-Martínez Teresa Ponce-Noyola 《Archives of microbiology》2014,196(1):25-33
The catalytic fraction of the Cellulomonas flavigena PN-120 oligomeric β-glucosidase (BGLA) was expressed both intra- and extracellularly in a recombinant diploid of Saccharomyces cerevisiae, under limited nutrient conditions. The recombinant enzyme (BGLA15) expressed in the supernatant of a rich medium showed 582 IU/L and 99.4 IU/g dry cell, with p-nitrophenyl-β-d-glucopyranoside as substrate. BGLA15 displayed activity against cello-oligosaccharides with 2–5 glucose monomers, demonstrating that the protein is not specific for cellobiose and that the oligomeric structure is not essential for β-d-1,4-bond hydrolysis. Native β-glucosidase is inhibited almost completely at 160 mM glucose, thus limiting cellobiose hydrolysis. At 200 mM glucose concentration, BGLA15 retained more than 50 % of its maximal activity, and even at 500 mM glucose concentration, more than 30 % of its activity was preserved. Due to these characteristics of BGLA15 activity, recombinant S. cerevisiae is able to utilize cellulosic materials (cello-oligosaccharides) to produce bioethanol. 相似文献
73.
Carlos E. Pedraza Christopher Taylor Albertina Pereira Michelle Seng Chui-Se Tham Michal Izrael Michael Webb 《ASN neuro》2014,6(4)
In inflammatory demyelinating diseases such as multiple sclerosis (MS), myelin
degradation results in loss of axonal function and eventual axonal degeneration.
Differentiation of resident oligodendrocyte precursor cells (OPCs) leading to
remyelination of denuded axons occurs regularly in early stages of MS but halts as
the pathology transitions into progressive MS. Pharmacological potentiation of
endogenous OPC maturation and remyelination is now recognized as a promising
therapeutic approach for MS. In this study, we analyzed the effects of modulating the
Rho-A/Rho-associated kinase (ROCK) signaling pathway, by the use of selective
inhibitors of ROCK, on the transformation of OPCs into mature, myelinating
oligodendrocytes. Here we demonstrate, with the use of cellular cultures from rodent
and human origin, that ROCK inhibition in OPCs results in a significant generation of
branches and cell processes in early differentiation stages, followed by accelerated
production of myelin protein as an indication of advanced maturation. Furthermore,
inhibition of ROCK enhanced myelin formation in cocultures of human OPCs and neurons
and remyelination in rat cerebellar tissue explants previously demyelinated with
lysolecithin. Our findings indicate that by direct inhibition of this signaling
molecule, the OPC differentiation program is activated resulting in morphological and
functional cell maturation, myelin formation, and regeneration. Altogether, we show
evidence of modulation of the Rho-A/ROCK signaling pathway as a viable target for the
induction of remyelination in demyelinating pathologies. 相似文献
74.
75.
Yusei Miyazaki Rui Li Ayman Rezk Hétoum Misirliyan Craig Moore Nasr Farooqi Mayra Solis Lorna Galleguillos Goiry Omar de Faria Junior Van Duc Dang David Colman Ajit Singh Dhaunchak Jack Antel Jennifer Gommerman Alexandre Prat Simon Fillatreau Amit Bar-Or 《PloS one》2014,9(8)
Clinical trial results demonstrating that B-cell depletion substantially reduces new relapses in patients with multiple sclerosis (MS) have established that B cells play a role in the pathophysiology of MS relapses. The same treatment appears not to impact antibodies directed against the central nervous system, which underscores the contribution of antibody-independent functions of B cells to disease activity. One mechanism by which B cells are now thought to contribute to MS activity is by over-activating T cells, including through aberrant expression of B cell pro-inflammatory cytokines. However, the mechanisms underlying the observed B cell cytokine dysregulation in MS remain unknown. We hypothesized that aberrant expression of particular microRNAs might be involved in the dysregulated pro-inflammatory cytokine responses of B cells of patients with MS. Through screening candidate microRNAs in activated B cells of MS patients and matched healthy subjects, we discovered that abnormally increased secretion of lymphotoxin and tumor necrosis factor α by MS B cells is associated with abnormally increased expression of miR-132. Over-expression of miR-132 in normal B cells significantly enhanced their production of lymphotoxin and tumor necrosis factor α. The over-expression of miR-132 also suppressed the miR-132 target, sirtuin-1. We confirmed that pharmacological inhibition of sirtuin-1 in normal B cells induces exaggerated lymphotoxin and tumor necrosis factor α production, while the abnormal production of these cytokines by MS B cells can be normalized by resveratrol, a sirtuin-1 activator. These results define a novel miR-132-sirtuin-1 axis that controls pro-inflammatory cytokine secretion by human B cells, and demonstrate that a dysregulation of this axis underlies abnormal pro-inflammatory B cell cytokine responses in patients with MS. 相似文献
76.
Decarli Monize Caiado dos Santos Diogo Peres Astray Renato Mancini Ventini-Monteiro Daniella Cristina Jorge Soraia Attie Calil Correia Daniela Matilde de Sá da Silva Juliana Rocca Mayra Pereira Langoni Hélio Menozzi Benedito Donizete Pereira Carlos Augusto Suazo Claudio Alberto Torres 《Applied microbiology and biotechnology》2018,102(11):4773-4783
Applied Microbiology and Biotechnology - The transmembrane rabies virus glycoprotein (RVGP) is the main antigen of vaccine formulations used around the world to prevent rabies, the most lethal... 相似文献
77.
78.
Absolute dependence on kappa B responsive elements for initiation and Tat-mediated amplification of HIV transcription in blood CD4 T lymphocytes. 下载免费PDF全文
79.
Jorge Morales Pedraza 《Cell and tissue banking》2016,17(2):179-188
A tissue establishment is a unit or service, inside or outside of a public or private hospital, generally operated by public or non-profit-making bodies or in some countries by private profit-making institutions that procure, process, sterilise, store, and distribute sterilised human tissues to private or public hospitals to be used in certain medical treatments. Each tissue establishment should adopt the best possible structure, hired the necessary well-trained staff, according to the level of its activities, and should establish the necessary internal committees to ensure the highest quality of its operation. In addition, the tissue establishment should adopt a quality management system in order to reduce the risk and maximize the benefits of the transplantation process. 相似文献
80.