全文获取类型
收费全文 | 288篇 |
免费 | 20篇 |
出版年
2022年 | 3篇 |
2021年 | 7篇 |
2020年 | 1篇 |
2019年 | 4篇 |
2018年 | 6篇 |
2017年 | 7篇 |
2016年 | 11篇 |
2015年 | 8篇 |
2014年 | 14篇 |
2013年 | 18篇 |
2012年 | 18篇 |
2011年 | 22篇 |
2010年 | 16篇 |
2009年 | 8篇 |
2008年 | 15篇 |
2007年 | 26篇 |
2006年 | 14篇 |
2005年 | 14篇 |
2004年 | 13篇 |
2003年 | 9篇 |
2002年 | 9篇 |
2001年 | 11篇 |
2000年 | 10篇 |
1999年 | 10篇 |
1998年 | 3篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 4篇 |
1990年 | 2篇 |
1988年 | 3篇 |
1987年 | 5篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1980年 | 2篇 |
1968年 | 1篇 |
1964年 | 2篇 |
1956年 | 1篇 |
排序方式: 共有308条查询结果,搜索用时 15 毫秒
261.
Jurelevicius D von der Weid I Korenblum E Valoni E Penna M Seldin L 《Journal of industrial microbiology & biotechnology》2008,35(4):251-255
Sulfide production by sulfate-reducing bacteria (SRB) is a major concern for the petroleum industry since it is toxic and
corrosive, and causes plugging due to the formation of insoluble iron sulfides (reservoir souring). In this study, PCR followed
by denaturing gradient gel electrophoresis (PCR-DGGE) using two sets of primers based on the 16S rRNA gene and on the aps gene (adenosine-5-phosphosulfate reductase) was used to track changes in the total bacterial and SRB communities, respectively,
present in the water-oil tank system on an offshore platform in Brazil in which nitrate treatment was applied for 2 months
(15 nitrate injections). PCR-DGGE analysis of the total bacterial community showed the existence of a dominant population
in the water-oil tank, and that the appearance and/or the increase of intensity of some bands in the gels were not permanently
affected by the introduction of nitrate. On the other hand, the SRB community was stimulated following nitrate treatment.
Moreover, sulfide production did not exceed the permissible exposure limit in the water-oil separation tank studied treated
with nitrate. Therefore, controlling sulfide production by treating the produced water tank with nitrate could reduce the
quantity of chemical biocides required to control microbial activities. 相似文献
262.
Guilherme L. de Oliveira Juliane F. Oliveira Júlia M. Pescarini Roberto F. S. Andrade Joilda S. Nery Maria Y. Ichihara Liam Smeeth Elizabeth B. Brickley Maurício L. Barreto Gerson O. Penna Maria L. F. Penna Mauro N. Sanchez 《PLoS neglected tropical diseases》2021,15(8)
BackgroundLeprosy remains concentrated among the poorest communities in low-and middle-income countries and it is one of the primary infectious causes of disability. Although there have been increasing advances in leprosy surveillance worldwide, leprosy underreporting is still common and can hinder decision-making regarding the distribution of financial and health resources and thereby limit the effectiveness of interventions. In this study, we estimated the proportion of unreported cases of leprosy in Brazilian microregions.Methodology/Principal findingsUsing data collected between 2007 to 2015 from each of the 557 Brazilian microregions, we applied a Bayesian hierarchical model that used the presence of grade 2 leprosy-related physical disabilities as a direct indicator of delayed diagnosis and a proxy for the effectiveness of local leprosy surveillance program. We also analyzed some relevant factors that influence spatial variability in the observed mean incidence rate in the Brazilian microregions, highlighting the importance of socioeconomic factors and how they affect the levels of underreporting. We corrected leprosy incidence rates for each Brazilian microregion and estimated that, on average, 33,252 (9.6%) new leprosy cases went unreported in the country between 2007 to 2015, with this proportion varying from 8.4% to 14.1% across the Brazilian States.Conclusions/SignificanceThe magnitude and distribution of leprosy underreporting were adequately explained by a model using Grade 2 disability as a marker for the ability of the system to detect new missing cases. The percentage of missed cases was significant, and efforts are warranted to improve leprosy case detection. Our estimates in Brazilian microregions can be used to guide effective interventions, efficient resource allocation, and target actions to mitigate transmission. 相似文献
263.
264.
The evolution of phenotypic integration: How directional selection reshapes covariation in mice
下载免费PDF全文
![点击此处可从《Evolution; international journal of organic evolution》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Anna Penna Diogo Melo Sandra Bernardi Maria Inés Oyarzabal Gabriel Marroig 《Evolution; international journal of organic evolution》2017,71(10):2370-2380
Variation is the basis for evolution, and understanding how variation can evolve is a central question in biology. In complex phenotypes, covariation plays an even more important role, as genetic associations between traits can bias and alter evolutionary change. Covariation can be shaped by complex interactions between loci, and this genetic architecture can also change during evolution. In this article, we analyzed mouse lines experimentally selected for changes in size to address the question of how multivariate covariation changes under directional selection, as well as to identify the consequences of these changes to evolution. Selected lines showed a clear restructuring of covariation in their cranium and, instead of depleting their size variation, these lines increased their magnitude of integration and the proportion of variation associated with the direction of selection. This result is compatible with recent theoretical works on the evolution of covariation that take the complexities of genetic architecture into account. This result also contradicts the traditional view of the effects of selection on available covariation and suggests a much more complex view of how populations respond to selection. 相似文献
265.
Penna G Giarratana N Amuchastegui S Mariani R Daniel KC Adorini L 《Microbes and infection / Institut Pasteur》2005,7(7-8):1033-1039
Dendritic cells (DCs) induce and regulate T-cell responses, and tolerogenic DCs can promote the development of regulatory T cells with suppressive activity. The possibility of manipulating DCs using different pharmacological or biological agents, enabling them to exert tolerogenic activities, could be exploited to better control a variety of chronic inflammatory conditions, from autoimmune diseases to allograft rejection. 相似文献
266.
Unique regulation of CCL18 production by maturing dendritic cells 总被引:10,自引:0,他引:10
Vulcano M Struyf S Scapini P Cassatella M Bernasconi S Bonecchi R Calleri A Penna G Adorini L Luini W Mantovani A Van Damme J Sozzani S 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(7):3843-3849
Dendritic cells (DC) orchestrate the trafficking of lymphocytes by secreting chemokines with different specificity and function. Chemokines are produced at higher levels by mature DC. This study shows that CCL18 is one of the most abundant chemokines produced by immature DC. In contrast to all other chemokines investigated to date, CCL18 was selectively down-regulated during the maturation process induced by LPS, TNF, CD40 ligand, Staphylococcus aureus Cowan I, Candida albicans, and influenza virus. IL-10 and vitamin D(3), two known inhibitors of DC differentiation and function, strongly promoted CCL18 secretion, whereas IFN-gamma, a costimulator of DC function, inhibited its production. IL-10 also induced CCL18 secretion in blood myeloid DC. No CCL18 secretion was observed in blood plasmacytoid DC. The opposite pattern of regulation was observed for CCL20, a prototypic inflammatory chemokine. CCL18 was found to be a chemotactic factor for immature DC. Therefore, CCL18 may act as a chemotactic signal that promotes the colocalization of immature DC with naive T lymphocytes in an IL-10-dominated environment with the consequent generation of T regulatory cells. These characteristics suggest that CCL18 may be part of an inhibitory pathway devoted to limiting the generation of specific immune responses at peripheral sites. 相似文献
267.
Cutting edge: differential chemokine production by myeloid and plasmacytoid dendritic cells 总被引:10,自引:0,他引:10
Penna G Vulcano M Roncari A Facchetti F Sozzani S Adorini L 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(12):6673-6676
To examine the different roles of myeloid dendritic cells (M-DCs) and plasmacytoid dendritic cells (P-DCs) in the induction and regulation of immune response, we have studied chemokine secretion by freshly isolated DC subsets in response to bacterial, viral, and T cell-derived stimuli. M-DCs selectively produced very high levels of the homeostatic chemokines CC chemokine ligand (CCL)17 and CCL22, while P-DCs produced very little if any. In contrast, the proinflammatory chemokine CCL3 was secreted mostly by P-DCs, whereas CCL4 and CXC chemokine ligand 8 were produced by both subsets. The selective production of CCL17 and CCL22 by M-DCs but not P-DCs was confirmed in vivo by immunohistology on human reactive lymph node sections. The high production of CCR4 ligands by M-DCs suggests their capacity to selectively recruit at sites of inflammation T cells with regulatory properties or with a Th2 phenotype, whereas P-DCs, by preferentially secreting CCR1/CCR5 ligands, would mostly recruit effector T cells and, in particular, Th1-type cells. 相似文献
268.
Dendritic cells (DCs) not only induce but also modulate T cell activation. 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] induces DCs with a tolerogenic phenotype, characterized by decreased expression of CD40, CD80, and CD86 costimulatory molecules, low IL-12 and enhanced IL-10 secretion. We have found that a short treatment with 1,25(OH)(2)D(3) induces tolerance to fully mismatched mouse islet allografts that is stable to challenge with donor-type spleen cells and allows acceptance of donor-type vascularized heart grafts. This effect is enhanced by co-administration of mycophenolate mofetil (MMF), a selective inhibitor of T and B cell proliferation that has also effects similar to 1,25(OH)(2)D(3) on DCs. Graft acceptance is associated with an increased percentage of CD4(+)CD25(+) regulatory cells in the spleen and in the draining lymph node that can protect 100% of syngeneic recipients from islet allograft rejection. CD4(+)CD25(+) cells, able to inhibit the T cell response to a pancreatic autoantigen and to significantly delay disease transfer by pathogenic CD4(+)CD25(-) cells, are also induced by treatment of adult nonobese diabetic (NOD) mice with 1,25-dihydroxy-16,23Z-diene-26,27-hexafluoro-19-nor vitamin D(3) (BXL-698). This treatment arrests progression of insulitis and Th1 cell infiltration, and inhibits diabetes development at non-hypercalcemic doses. The enhancement of CD4(+)CD25(+) regulatory T cells, able to mediate transplantation tolerance and to arrest type 1 diabetes development by a short oral treatment with VDR ligands, suggests possible clinical applications of this approach. 相似文献
269.
Nitroxyl affords thiol-sensitive myocardial protective effects akin to early preconditioning 总被引:8,自引:0,他引:8
Pagliaro P Mancardi D Rastaldo R Penna C Gattullo D Miranda KM Feelisch M Wink DA Kass DA Paolocci N 《Free radical biology & medicine》2003,34(1):33-43
Nitric oxide (NO) donors mimic the early phase of ischemic preconditioning (IPC). The effects of nitroxyl (HNO/NO(-)), the one-electron reduction product of NO, on ischemia/reperfusion (I/R) injury are unknown. Here we investigated whether HNO/NO(-), produced by decomposition of Angeli's salt (AS; Na(2)N(2)O(3)), has a cardioprotective effect in isolated perfused rat hearts. Effects were examined after intracoronary perfusion (19 min) of either AS (1 microM), the NO donor diethylamine/NO (DEA/NO, 0.5 microM), vehicle (100 nM NaOH) or buffer, followed by global ischemia (30 min) and reperfusion (30 min or 120 min in a subset of hearts). IPC was induced by three cycles of 3 min ischemia followed by 10 min reperfusion prior to I/R. The extent of I/R injury under each intervention was assessed by changes in myocardial contractility as well as lactate dehydrogenase (LDH) release and infarct size. Postischemic contractility, as indexed by developed pressure and dP/dt(max), was similarly improved with IPC and pre-exposure to AS, as opposed to control or DEA/NO-treated hearts. Infarct size and LDH release were also significantly reduced in IPC and AS groups, whereas DEA/NO was less effective in limiting necrosis. Co-infusion in the triggering phase of AS and the nitroxyl scavenger, N-acetyl-L-cysteine (4 mM) completely reversed the beneficial effects of AS, both at 30 and 120 min reperfusion. Our data show that HNO/NO(-) affords myocardial protection to a degree similar to IPC and greater than NO, suggesting that reactive nitrogen oxide species are not only necessary but also sufficient to trigger myocardial protection against reperfusion through species-dependent, pro-oxidative, and/or nitrosative stress-related mechanisms. 相似文献
270.
Wang J Della Penna K Wang H Karczewski J Connolly TM Koblan KS Bennett PB Salata JJ 《American journal of physiology. Heart and circulatory physiology》2003,284(1):H256-H267
We established HEK-293 cell lines that stably express functional canine ether-à-go-go-related gene (cERG) K(+) channels and examined their biophysical and pharmacological properties with whole cell patch clamp and (35)S-labeled MK-499 ([(35)S]MK-499) binding displacement. Functionally, cERG current had the hallmarks of cardiac delayed rectifier K(+) current (I(Kr)). Channel opening was time- and voltage dependent with threshold near -40 mV. The half-maximum activation voltage was -7.8 +/- 2.4 mV at 23 degrees C, shifting to -31.9 +/- 1.2 mV at 36 degrees C. Channels activated with a time constant of 13 +/- 1 ms at +20 mV, showed prominent inward rectification at depolarized potentials, were highly K(+) selective (Na(+)-to-K(+) permeability ratio = 0.007), and were potently inhibited by I(Kr) blockers. Astemizole, terfenadine, cisapride, and MK-499 inhibited cERG and human ERG (hERG) currents with IC(50) values of 1.3, 13, 19, and 15 nM and 1.2, 9, 14, and 21 nM, respectively, and competitively displaced [(35)S]MK-499 binding from cERG and hERG with IC(50) values of 0.4, 12, 35, and 0.6 nM and 0.8, 5, 47, and 0.7 nM, respectively. cERG channels had biophysical properties appropriate for canine action potential repolarization and were pharmacologically sensitive to agents known to prolong QT. A novel MK-499 binding assay provides a new tool to detect agents affecting ERG channels. 相似文献