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71.
Microglia modulation through external vagus nerve stimulation in a murine model of Alzheimer's disease 下载免费PDF全文
Robert Kaczmarczyk Dario Tejera Bruce J. Simon Michael T. Heneka 《Journal of neurochemistry》2018,146(1):76-85
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Marleen TJ van Ampting Arjan J Schonewille Carolien Vink Robert Jan M Brummer van der Roelof Meer Ingeborg MJ Bovee-Oudenhoven 《BMC physiology》2009,9(1):6-9
Background
Glutathione, the main antioxidant of intestinal epithelial cells, is suggested to play an important role in gut barrier function and prevention of inflammation-related oxidative damage as induced by acute bacterial infection. Most studies on intestinal glutathione focus on oxidative stress reduction without considering functional disease outcome. Our aim was to determine whether depletion or maintenance of intestinal glutathione changes susceptibility of rats to Salmonella infection and associated inflammation. 相似文献74.
Michael Honer Thomas Ebenhan Peter R Allegrini Simon M Ametamey Mike Becquet Catherine Cannet Heidi A Lane Terence M O'Reilly Pius A Schubiger Melanie Sticker-Jantscheff Michael Stumm Paul MJ McSheehy 《Translational oncology》2010,3(4):264-275
Noninvasive functional imaging of tumors can provide valuable early-response biomarkers, in particular, for targeted chemotherapy. Using various experimental tumor models, we have investigated the ability of positron emission tomography (PET) measurements of 2-deoxy-2-[18F]fluoro-glucose (FDG) and 3′-deoxy-3′-[18F]fluorothymidine (FLT) to detect response to the allosteric mammalian target of rapamycin (mTOR) inhibitor everolimus. Tumor models were declared sensitive (murine melanoma B16/BL6 and human lung H596) or relatively insensitive (human colon HCT116 and cervical KB31), according to the IC50 values (concentration inhibiting cell growth by 50%) for inhibition of proliferation in vitro (<10 nM and >1 µM, respectively). Everolimus strongly inhibited growth of the sensitive models in vivo but also significantly inhibited growth of the insensitive models, an effect attributable to its known anti-angiogenic/vascular properties. However, although tumor FDG and FLT uptake was significantly reduced in the sensitive models, it was not affected in the insensitive models, suggesting that endothelial-directed effects could not be detected by these PET tracers. Consistent with this hypothesis, in a well-vascularized orthotopic rat mammary tumor model, other antiangiogenic agents also failed to affect FDG uptake, despite inhibiting tumor growth. In contrast, the cytotoxic patupilone, a microtubule stabilizer, blocked tumor growth, and markedly reduced FDG uptake. These results suggest that FDG/FLT-PET may not be a suitable method for early markers of response to antiangiogenic agents and mTOR inhibitors in which anti-angiogenic/vascular effects predominate because the method could provide false-negative responses. These conclusions warrant clinical testing. 相似文献
75.
Background
A vast number of biomechanical studies have employed inverse dynamics methods to calculate inter-segmental moments during movement. Although all inverse dynamics methods are rooted in classical mechanics and thus theoretically the same, there exist a number of distinct computational methods. Recent research has demonstrated a key influence of the dynamics computation of the inverse dynamics method on the calculated moments, despite the theoretical equivalence of the methods. The purpose of this study was therefore to explore the influence of the choice of inverse dynamics on the calculation of inter-segmental moments. 相似文献76.
77.
Background
Ensemble attribute profile clustering is a novel, text-based strategy for analyzing a user-defined list of genes and/or proteins. The strategy exploits annotation data present in gene-centered corpora and utilizes ideas from statistical information retrieval to discover and characterize properties shared by subsets of the list. The practical utility of this method is demonstrated by employing it in a retrospective study of two non-overlapping sets of genes defined by a published investigation as markers for normal human breast luminal epithelial cells and myoepithelial cells. 相似文献78.
Irfan Y. Tamboli Esther Barth Leonie Christian Martin Siepmann Sathish Kumar Sandesh Singh Karen Tolksdorf Michael T. Heneka Dieter Lütjohann Patrick Wunderlich Jochen Walter 《The Journal of biological chemistry》2010,285(48):37405-37414
Epidemiological studies indicate that intake of statins decrease the risk of developing Alzheimer disease. Cellular and in vivo studies suggested that statins might decrease the generation of the amyloid β-peptide (Aβ) from the β-amyloid precursor protein. Here, we show that statins potently stimulate the degradation of extracellular Aβ by microglia. The statin-dependent clearance of extracellular Aβ is mainly exerted by insulin-degrading enzyme (IDE) that is secreted in a nonconventional pathway in association with exosomes. Stimulated IDE secretion and Aβ degradation were also observed in blood of mice upon peripheral treatment with lovastatin. Importantly, increased IDE secretion upon lovastatin treatment was dependent on protein isoprenylation and up-regulation of exosome secretion by fusion of multivesicular bodies with the plasma membrane. These data demonstrate a novel pathway for the nonconventional secretion of IDE via exosomes. The modulation of this pathway could provide a new strategy to enhance the extracellular clearance of Aβ. 相似文献
79.
Sandrine MJ. Camus Céline Rochais Catherine Blois-Heulin Qin Li Martine Hausberger Erwan Bezard 《PloS one》2013,8(7)
Background
Adverse early-life experience might lead to the expression of abnormal behaviours in animals and the predisposition to psychiatric disorder (e.g. major depressive disorder) in Humans. Common breeding processes employ weaning and housing conditions different from what happens in the wild.Methods
The present study, therefore, investigated whether birth origin impacts the possible existence of spontaneous atypical/abnormal behaviours displayed by 40 captive-born and 40 wild-born socially-housed cynomolgus macaques in farming conditions using an unbiased ethological scan-sampling analysis followed by multifactorial correspondence and hierarchical clustering analyses.Results
We identified 10 distinct profiles (groups A to J) that significantly differed on several behaviours, body postures, body orientations, distances between individuals and locations in the cage. Data suggest that 4 captive-born and 1 wild-born animals (groups G and J) present depressive-like symptoms, unnatural early life events thereby increasing the risk of developing pathological symptoms. General differences were also highlighted between the captive- and wild-born populations, implying the expression of differential coping mechanisms in response to the same captive environment.Conclusions
Birth origin thus impacts the development of atypical ethologically-defined behavioural profiles, reminiscent of certain depressive-like symptoms. The use of unbiased behavioural observations might allow the identification of animal models of human mental/behavioural disorders and their most appropriate control groups. 相似文献80.
Terwel D Löschmann YN Schmidt HH Schöler HR Cantz T Heneka MT 《Journal of neurochemistry》2011,118(1):105-112
Wilson's disease (WD) is caused by mutations in the copper transporting ATPase 7B (Atp7b). Patients present with liver pathology or behavioural disturbances. Studies on rodent models for WD so far mainly focussed on liver, not brain. The effect of knockout of atp7b on sensori-motor and cognitive behaviour, as well as neuronal number, inflammatory markers, copper and synaptic proteins in brain were studied in so-called toxic milk mice. Copper accumulated in striatum and hippocampus of toxic milk mice, but not in cerebral cortex. Inflammatory markers were increased in striatum and corpus callosum, but not in cerebral cortex and hippocampus, whereas neuronal numbers were unchanged. Toxic milk mice were mildly impaired in the rotarod and cylinder test and unable to acquire spatial memory in the Morris water maze. Despite the latter observation only synaptophysin of a number of synaptic proteins, was altered in the hippocampus of toxic milk mice. In addition to disturbances in neuronal signalling by increased brain copper, inflammation and inflammatory signalling from the periphery to the brain might add to the behavioural disturbances in the toxic milk mice. These mice can be used to evaluate therapeutic strategies to alleviate behavioural disturbances and cerebral pathology observed in WD. 相似文献