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1.
M1 protein triggers a phosphoinositide cascade for group A Streptococcus invasion of epithelial cells
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Invasion of nonphagocytic cells by bacteria provides a favorable niche for persistence and evasion of host defenses and antibiotics. M protein is a major virulence factor because it promotes high-frequency invasion of epithelial cells by group A Streptococcus (GAS) and also renders the bacterium resistant to phagocytosis. In this study, we investigated the role of M1 protein from serotype M1 strain 90-226 in regulating mammalian signal transduction and cytoskeletal rearrangement for bacterial entry. LY294002 and wortmannin, which are inhibitors of phosphatidylinositol 3-kinase (PI 3-K) blocked invasion of epithelial cells by GAS by 75 and 80%, respectively, but failed to inhibit invasion by Salmonella enterica serovar Typhimurium. Also, epithelial cells transiently transfected with dominant negative p85 and p110 genes, the regulatory and catalytic subunits of PI 3-K, respectively, were less able to be invaded by GAS. To separate the influence of other streptococcal virulence factors from M protein, Lactococcus lactis was engineered to express M1 protein on its surface. L. lactis(pLM1) invaded epithelial cells efficiently in vitro, and PI 3-K inhibitors blocked 90% of this invasion. Purified soluble M1 protein stimulated the formation of stress fibers and actin tuffs on epithelial cells. LY294002 and wortmannin inhibited these cellular changes. A phosphoinositide analogue also inhibited the invasion of epithelial cells by GAS. Therefore, M1 protein, either directly or via bound fibronectin, initiates signals that depend on the lipid kinase PI 3-K pathway, which paves the way for cytoskeletal rearrangement that internalize the bacterium. 相似文献
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The group B streptococcus (GBS) is a major cause of pneumonia, sepsis, and meningitis in neonates and a serious cause of mortality or morbidity in immunocompromised adults. Although these streptococci adhere efficiently and invade a variety of tissue-specific epithelial and endothelial cells, adhesins and invasins are still unknown. All serotypes of GBS studied to date express C5a peptidase (SCPB) on their surface. This investigation addresses the possibility that this relatively large surface protein has additional activities. Rabbit anti-SCPB serum inhibited invasion of lung epithelial A549 cells by the serotype Ia strain O90R, suggesting that SCPB is an invasin. This was confirmed by inserting an in-frame 25-amino-acid deletion into the scpB gene. Invasion of HEp2 and A549 human cell lines was significantly reduced by the mutation. Enzyme-linked immunosorbent assays were used to demonstrate that purified SCPB protein binds directly to HEp2 and A549 cells and also binds the extracellular matrix protein fibronectin. Binding was dose dependent and saturable. These results suggested that SCPB is one of several potential invasins essential for GBS colonization of damaged epithelium. 相似文献
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Thirumalaiandi Ramasubramanian Mariappan Paramasivam Kallolathu Purushothaman Salin Ramabhadran Jayanthi 《Bulletin of environmental contamination and toxicology》2012,89(6):1268-1271
Dissipation kinetics of chlorantraniliprole was studied in sandy loam soils of sugarcane ecosystem by adopting a rapid analytical method. The recovery of chlorantraniliprole was 91.67 % when extracted with ethyl acetate as against only 65.58 % in acetonitrile-based extraction. An additional cleanup step with primary secondary amine did not enhance the recovery significantly over the no-cleanup method. The ethyl acetate-based extraction followed by direct quantification in HPLC (High-performance liquid chromatography) without any cleanup facilitated rapid quantification of chlorantraniliprole residues. The LOQ (limit of quantification) of the method was 0.01 μg/g. The half-life of chlorantraniliprole was 6.50 and 6.81 days for the recommended and double the recommended doses, respectively. 相似文献
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Antibody GD3G7 selected against embryonic glycosaminoglycans defines chondroitin sulfate-E domains highly up-regulated in ovarian cancer and involved in vascular endothelial growth factor binding 总被引:1,自引:0,他引:1
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ten Dam GB van de Westerlo EM Purushothaman A Stan RV Bulten J Sweep FC Massuger LF Sugahara K van Kuppevelt TH 《The American journal of pathology》2007,171(4):1324-1333
Chondroitin sulfate (CS) is abundantly present in the tumor stroma, and tumor-specific CS modifications might be potential targets to influence tumor development. We applied the phage display technology to select antibodies that identify these tumor-specific CS modifications. Antibody GD3G7 was selected against embryonic glycosaminoglycans, and it reacted strongly with CS-E (rich in GlcA-GalNAc4S6S units). In ovarian adenocarcinomas, strong expression of this CS-E epitope was found in the extracellular matrix, and occasionally on tumor cells. No expression was found in normal ovary and cystadenomas. Differential expression was found in ovarian carcinoma cell lines, which correlated with the gene expression of the GalNAc4S-6st enzyme, involved in biosynthesis of CS-E. Vascular endothelial growth factor (VEGF)-sensitive fenestrated (in normal tissues) and tumor blood vessels were both identified by antibody GD3G7, which might implicate a role for CS-E in VEGF biology. VEGF bound to CS-E and antibody GD3G7 could compete for binding of VEGF to CS-E. In conclusion, antibody GD3G7 identified rare CS-E-like structures that were strongly expressed in ovarian adenocarcinomas. This antibody might therefore be instrumental for identifying tumor-related CS alterations. 相似文献
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Back pain and spinal deformity are the most common presenting complaints of spinal disorders in childhood seen in a specialist orthopaedic spinal clinic. Many of the patients referred will have non-specific back pain, yet there are a multitude of significant and sinister pathologies of the spine along with extraspinal causes that should be considered and sought. Similarly most deformities will be either minor or idiopathic, yet specific underlying causes need to be excluded. The cornerstone of safe practice is a detailed, thorough and targeted history and examination. This article focuses on painful disorders. 相似文献
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AbstractThe development of computer modeling technique of cerebral arteriovenous malformations using circuit network analysis, validated with a previously developed animal model is presented. Such a malformation and its vascular connections are rendered into a complex system of interconnecting tubes; which is then simulated by an analogous electrical circuit using commercially available computer software. This methodology was tested using a swine model, of which a detailed computer model was constructed from anatomic and angiographic measurements of the cranial vessels. Flow conditions, before and after creation of the in vivo model, were predicted from the computer model and compared with previously reported in vivo measurements. Detailed analysis of flow within the CAVM nidus was also performed. There was a good correlation between the computer and in vivo models regarding changes in flow and pressure drop across the rete. Flow mapping within the nidus showed localized directional flow that was determined by global inputs, consistent with functional compartmental ization. This method of computer modeling appears promising for studying clinically relevant aspects of cerebral arteriovenous malformation pathophysiology. To our knowledge it is the first computer model to demonstrate functional compartmentalization. [Neurol Res 1996; 18: 361-366] 相似文献
10.
BACKGROUND: Recent discussions on the relationship between intracranial aneurysm diameter and rupture probability have focused on the presence of an apparent critical diameter of 10 mm for aneurysm rupture. Despite the fact that many investigators have argued against the existence of this critical diameter, no one has yet proposed a viable alternative concept. In this report we present a scientifically rigorous alternative concept, that the size-specific rupture probability (RP) of an aneurysm varies as the third power of the aneurysm diameter. METHODS: We utilized a new biophysical model of aneurysm rupture that predicts the relationship between the size-specific rupture probability of an aneurysm and the diameter (D) to be RP = kD(3). We tested this hypothesis against data from two autopsy studies and one large clinical aneurysm study. Subsequently, using this D(3) hypothesis and the different size distributions of aneurysms in the study populations, we predicted the variation of cumulative rupture probability (CRP) with diameter for each population. RESULTS: Data from the autopsy studies supported the diameter-cube hypothesis, with the log-log plots of size-specific rupture probability versus aneurysm diameter from the two autopsy series yielding lines with slopes 3.54 (R(2) = 0.61, p < 0.12) and 3.05 (R(2) = 0.98, p < 0.001). Plots of cumulative rupture probability versus diameter were determined to be sensitive to the size distributions of the unruptured aneurysms in the population. Furthermore, none of the CRP plots showed evidence of a critical diameter for aneurysm rupture. CONCLUSIONS: RP varies as the third power of aneurysm diameter, a relationship that predicts a continuous increase in RP with increasing size rather than the existence of a threshold diameter that separates low- from high-risk aneurysms. Accordingly, all aneurysms have finite risk for rupture and deserve consideration for treatment. Much of the current controversy regarding the relationship between rupture rates and diameter is a result of different size distributions in study populations rather than differences in aneurysm biology. 相似文献