全文获取类型
收费全文 | 276篇 |
免费 | 19篇 |
出版年
2022年 | 2篇 |
2021年 | 7篇 |
2020年 | 7篇 |
2019年 | 5篇 |
2018年 | 3篇 |
2017年 | 3篇 |
2016年 | 11篇 |
2015年 | 15篇 |
2014年 | 15篇 |
2013年 | 12篇 |
2012年 | 13篇 |
2011年 | 14篇 |
2010年 | 6篇 |
2009年 | 10篇 |
2008年 | 12篇 |
2007年 | 21篇 |
2006年 | 9篇 |
2005年 | 7篇 |
2004年 | 8篇 |
2003年 | 8篇 |
2002年 | 5篇 |
2001年 | 6篇 |
2000年 | 3篇 |
1999年 | 6篇 |
1998年 | 2篇 |
1997年 | 5篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 6篇 |
1992年 | 3篇 |
1991年 | 1篇 |
1990年 | 4篇 |
1989年 | 9篇 |
1988年 | 7篇 |
1987年 | 5篇 |
1986年 | 6篇 |
1985年 | 3篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1982年 | 5篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1972年 | 1篇 |
1971年 | 2篇 |
1967年 | 1篇 |
排序方式: 共有295条查询结果,搜索用时 15 毫秒
81.
Moalli F Paroni M Véliz Rodriguez T Riva F Polentarutti N Bottazzi B Valentino S Mantero S Nebuloni M Mantovani A Bragonzi A Garlanda C 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(9):5425-5434
Chronic lung infections by Pseudomonas aeruginosa strains are a major cause of morbidity and mortality in cystic fibrosis (CF) patients. Although there is no clear evidence for a primary defect in the immune system of CF patients, the host is generally unable to clear P. aeruginosa from the airways. PTX3 is a soluble pattern recognition receptor that plays nonredundant roles in the innate immune response to fungi, bacteria, and viruses. In particular, PTX3 deficiency is associated with increased susceptibility to P. aeruginosa lung infection. To address the potential therapeutic effect of PTX3 in P. aeruginosa lung infection, we established persistent and progressive infections in mice with the RP73 clinical strain RP73 isolated from a CF patient and treated them with recombinant human PTX3. The results indicated that PTX3 has a potential therapeutic effect in P. aeruginosa chronic lung infection by reducing lung colonization, proinflammatory cytokine levels (CXCL1, CXCL2, CCL2, and IL-1β), and leukocyte recruitment in the airways. In models of acute infections and in in vitro assays, the prophagocytic effect of PTX3 was maintained in C1q-deficient mice and was lost in C3- and Fc common γ-chain-deficient mice, suggesting that facilitated recognition and phagocytosis of pathogens through the interplay between complement and FcγRs are involved in the therapeutic effect mediated by PTX3. These data suggested that PTX3 is a potential therapeutic tool in chronic P. aeruginosa lung infections, such as those seen in CF patients. 相似文献
82.
Thymidine and deoxyuridine accumulate in tissues of patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) 总被引:2,自引:0,他引:2
Valentino ML Martí R Tadesse S López LC Manes JL Lyzak J Hahn A Carelli V Hirano M 《FEBS letters》2007,581(18):3410-3414
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disease due to ECGF1 gene mutations causing thymidine phosphorylase (TP) deficiency. Analysis of post-mortem samples of five MNGIE patients and two controls, revealed TP activity in all control tissues, but not in MNGIE samples. Converse to TP activity, thymidine and deoxyuridine were absent in control samples, but present in all tissues of MNGIE patients. Concentrations of both nucleosides in the tissues were generally higher than those observed in plasma of MNGIE patients. Our observations indicate that in the absence of TP activity, tissues accumulate nucleosides, which are excreted into plasma. 相似文献
83.
Miele C Paturzo F Teperino R Sakane F Fiory F Oriente F Ungaro P Valentino R Beguinot F Formisano P 《The Journal of biological chemistry》2007,282(44):31835-31843
Although chronic hyperglycemia reduces insulin sensitivity and leads to impaired glucose utilization, short term exposure to high glucose causes cellular responses positively regulating its own metabolism. We show that exposure of L6 myotubes overexpressing human insulin receptors to 25 mm glucose for 5 min decreased the intracellular levels of diacylglycerol (DAG). This was paralleled by transient activation of diacylglycerol kinase (DGK) and of insulin receptor signaling. Following 30-min exposure, however, both DAG levels and DGK activity returned close to basal levels. Moreover, the acute effect of glucose on DAG removal was inhibited by >85% by the DGK inhibitor R59949. DGK inhibition was also accompanied by increased protein kinase C-alpha (PKCalpha) activity, reduced glucose-induced insulin receptor activation, and GLUT4 translocation. Glucose exposure transiently redistributed DGK isoforms alpha and delta, from the prevalent cytosolic localization to the plasma membrane fraction. However, antisense silencing of DGKdelta, but not of DGKalpha expression, was sufficient to prevent the effect of high glucose on PKCalpha activity, insulin receptor signaling, and glucose uptake. Thus, the short term exposure of skeletal muscle cells to glucose causes a rapid induction of DGK, followed by a reduction of PKCalpha activity and transactivation of the insulin receptor signaling. The latter may mediate, at least in part, glucose induction of its own metabolism. 相似文献
84.
Over the last 15 years, important research has expanded our knowledge of the clinical, molecular genetic, and biochemical
features of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). The characterization of mitochondrial involvement
in this disorder and the seminal determination of its genetic cause, have opened new possibilities for more detailed and deeper
studies on the pathomechanisms in this progressive and fatal disease. It has been established that MNGIE is caused by mutations
in the gene encoding thymidine phosphorylase (TP), which lead to absolute or nearly complete loss of its catalytic activity,
producing systemic accumulations of its substrates, thymidine (dThd) and deoxyuridine (dUrd). Findings obtained from in vitro
and in vivo studies indicate that the biochemical imbalances specifically impair mitochondrial DNA (mtDNA) replication, repair,
or both leading to mitochondrial dysfunction. We have proposed that therapy for MNGIE should be aimed at reducing the concentrations
of these toxic nucleosides to normal or nearly normal levels. The first treatment, allogeneic stem-cell transplantation (alloSCT)
reported in 2006, produced a nearly full biochemical correction of the dThd and dUrd imbalances in blood. Clinical follow-up
of this and other patients receiving alloSCT is necessary to determine whether this and other therapies based on a permanent
restoration of TP will be effective treatment for MNGIE. 相似文献
85.
Real-Time PCR Investigation of Potential Vectors, Reservoirs, and Shedding Patterns of Feline Hemotropic Mycoplasmas 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Applied microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Barbara Willi Felicitas S. Boretti Marina L. Meli Marco V. Bernasconi Simona Casati Daniel Hegglin Maria Puorger Harold Neimark Valentino Cattori Nicole Wengi Claudia E. Reusch Hans Lutz Regina Hofmann-Lehmann 《Applied microbiology》2007,73(12):3798-3802
Three hemotropic mycoplasmas have been identified in pet cats: Mycoplasma haemofelis, “Candidatus Mycoplasma haemominutum,” and “Candidatus Mycoplasma turicensis.” The way in which these agents are transmitted is largely unknown. Thus, this study aimed to investigate fleas, ticks, and rodents as well as saliva and feces from infected cats for the presence of hemotropic mycoplasmas, to gain insight into potential transmission routes for these agents. DNA was extracted from arthropods and from rodent blood or tissue samples from Switzerland and from salivary and fecal swabs from two experimentally infected and six naturally infected cats. All samples were analyzed with real-time PCR, and some positive samples were confirmed by sequencing. Feline hemotropic mycoplasmas were detected in cat fleas and in a few Ixodes sp. and Rhipicephalus sp. ticks collected from animals but not in ticks collected from vegetation or from rodent samples, although the latter were frequently Mycoplasma coccoides PCR positive. When shedding patterns of feline hemotropic mycoplasmas were investigated, “Ca. Mycoplasma turicensis” DNA was detected in saliva and feces at the early but not at the late phase of infection. M. haemofelis and “Ca. Mycoplasma haemominutum” DNA was not amplified from saliva and feces of naturally infected cats, despite high hemotropic mycoplasma blood loads. Our results suggest that besides an ostensibly indirect transmission by fleas, direct transmission through saliva and feces at the early phase of infection could play a role in the epizootiology of feline hemotropic mycoplasmas. Neither the investigated tick nor the rodent population seems to represent a major reservoir for feline hemotropic mycoplasmas in Switzerland. 相似文献
86.
Hernández Pérez A E Cerna Chávez JC Delgado Ortiz M Beltrán Beache LM Tapia Vargas YM Ochoa Fuentes 《Phyton》2019,88(1):11-13
Mexico is the main producer, consumer and exporter
of avocado in the world, being Michoacan the main producer state
contributing more than 80% of the national production. There
are phytopathogens that decimate the production causing the
death of the tree. Root samples were collected in avocado trees
that showed the characteristic symptomatology of the disease
known as avocado sadness, the sampling was carried out in four
of the main avocado producing towns, in the state of Michoacan,
Mexico. The isolation consisted in sowing root tissue in Petri
dishes with V8®-PARPH culture medium, subsequently they were
identified morphologically and for species level it was determined
by molecular biology, with the PCR-ITS technique. Pathogenicity
tests were performed in triplicate with avocado seedlings with more
than six leaves. After 24 hours, the inoculated plants expressed
decay in the apical part, after 120 hours the leaves showed yellowing
and after 15 days there was a generalized wilt on the stem and
leaves, re-isolating the phytopathogen Phytopythium vexans.
This study confirms the first report of the oomycete P. vexans
affecting avocado trees in the most important producing region of
the Mexican Republic. 相似文献
87.
88.
Raffaela Pero Dario Palmieri Tiziana Angrisano Teresa Valentino Antonella Federico Renato Franco Francesca Lembo Andres J. Klein-Szanto Luigi Del Vecchio Donatella Montanaro Simona Keller Claudio Arra Vasiliki Papadopoulou Simon D. Wagner Carlo M. Croce Alfredo Fusco Lorenzo Chiariotti Monica Fedele 《The Journal of biological chemistry》2014,289(21):14966
89.
Herbivory is a fundamental process determining reef resilience, and while algal farming damselfishes can help shape benthic assemblages, an understanding of their contribution to areas outside of defended territories is relatively unexplored. Here, we demonstrate how the farming damselfish Stegastes marginatus plays a dual role in benthic structuring by 1) contributing to persistence of the invasive macroalga Acanthophora spicifera within a Hawaiian marine protected area, where the macroalga occurred exclusively inside Stegastes territories, and 2) behaving as an opportunistic browser of the exotic alga outside their territorial borders. Greater than 50% of the biomass of tethered A. spicifera was consumed within one-hour when placed outside Stegastes territories, compared to <5% lost from tethers within territories or herbivore exclusion cages. In situ remote video revealed that tethered A. spicifera located outside territories was grazed primarily by the surgeonfish Acanthurus nigrofuscus (∼68% of total bites) and, surprisingly, by S. marginatus (∼27% of total bites) that left their territories to feed on this resource on 107 occasions during 400 min of filming. Further, for over half of those occurrences where S. marginatus grazed on the tethered macroalga outside of territories, they fed alongside conspecifics and other species, displaying little of the aggressiveness that characterizes this damselfish. These results show that S. marginatus plays a wider role in determining benthic assemblages than previously recognized, acting both as cultivators of a canopy-forming invasive macroalga within their territories, and as opportunistic browsers in neighboring sites. Consequently, S. marginatus can affect benthic species composition across their territory borders. These results provide a rare example of interspecific facilitation of an exotic alga by an indigenous marine fish. Accounting for fish behaviors more broadly is important to further our understanding of ecological processes that shape reef ecosystems to improve management of MPAs that often support extensive farming damselfish populations. 相似文献
90.
Giovanni Rizzo Kevin R. Tozer Caterina Tonon David Manners Claudia Testa Emil Malucelli Maria Lucia Valentino Chiara La Morgia Piero Barboni Ruvdeep S. Randhawa Fred N. Ross-Cisneros Alfredo A. Sadun Valerio Carelli Raffaele Lodi 《PloS one》2012,7(11)
Leber’s hereditary optic neuropathy (LHON) is characterized by retinal ganglion cell (RGC) degeneration with the preferential involvement of those forming the papillomacular bundle. The optic nerve is considered the main pathological target for LHON. Our aim was to investigate the possible involvement of the post-geniculate visual pathway in LHON patients. We used diffusion-weighted imaging for in vivo evaluation. Mean diffusivity maps from 22 LHON visually impaired, 11 unaffected LHON mutation carriers and 22 healthy subjects were generated and compared at level of optic radiation (OR). Prefrontal and cerebellar white matter were also analyzed as internal controls. Furthermore, we studied the optic nerve and the lateral geniculate nucleus (LGN) in post-mortem specimens obtained from a severe case of LHON compared to an age-matched control. Mean diffusivity values of affected patients were higher than unaffected mutation carriers (P<0.05) and healthy subjects (P<0.01) in OR and not in the other brain regions. Increased OR diffusivity was associated with both disease duration (B = 0.002; P<0.05) and lack of recovery of visual acuity (B = 0.060; P<0.01). Post-mortem investigation detected atrophy (41.9% decrease of neuron soma size in the magnocellular layers and 44.7% decrease in the parvocellular layers) and, to a lesser extent, degeneration (28.5% decrease of neuron density in the magnocellular layers and 28.7% decrease in the parvocellular layers) in the LHON LGN associated with extremely severe axonal loss (99%) in the optic nerve. The post-geniculate involvement in LHON patients is a downstream post-synaptic secondary phenomenon, reflecting de-afferentation rather than a primary neurodegeneration due to mitochondrial dysfunction of LGN neurons. 相似文献