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111.
Increased Neurite Outgrowth Induced by Inhibition of Protein Tyrosine Kinase Activity in PC12 Pheochromocytoma Cells 总被引:7,自引:1,他引:6
Abstract: Genistein and other inhibitors of protein tyrosine kinases were examined for effects on neurite elongation and growth cone morphology in the rat PC12 pheochromocytoma cell line. Genistein increased the rate of neurite elongation in PC12 cells grown on a collagen/polylysine substratum after priming with nerve growth factor (NGF), but had no effect on undifferentiated cells. Steady-state levels of phosphotyrosine-modified proteins (105, 59, 52, and 46 kDa) were reduced in NGF-primed cells by genistein treatment. The target of genistein action did not appear to be the NGF receptor/ trk tyrosine kinase because the presence of NGF in cultures of NGF-primed cells was not necessary for genistein-stimulated neurite outgrowth. The tyrosine kinase inhibitors tyrphostin RG508964 and herbimycin A also increased the rate of neurite elongation in NGF-primed PC12 cells. Video-enhanced differential interference contrast microscopy revealed that growth cones of genistein-treated cells had less complex morphologies and were less dynamic than untreated cells, with short filopodia restricted to the leading edge, unlike untreated cells whose growth cones exhibited longer, more numerous filopodia and lamellipodia, which remodeled continuously. These results suggest that protein tyrosine kinase activity in PC12 cells negatively regulates neurite outgrowth and directly or indirectly affects growth cone morphology. 相似文献
112.
The song system of zebra finches is sexually dimorphic: the volumes of the song control nuclei and the neurons within these nuclei are larger in males. The song system of hatching female zebra finches is masculinized by systemic treatment with estrogen. We investigated the locus of this estrogen action by using microimplants of estradiol benzoate (EB). We implanted female zebra finch nestlings 10–13 days old with Silastic pellets containing approximately 2 μg EB at one of several sites: near the higher vocal center (HVC), in the brain distant from HVC, or in the periphery either under the skin of the breast or in the peritoneal cavity. Controls were either unimplanted or implanted near HVC with Silastic pellets without hormone. The brains were fixed by perfusion at 60 days, and the volumes of the song control regions as well as the sizes of individual neurons were measured. Neurons in HVC were lerger (more masculine) in the HVC-implanted group than in other groups, which did not differ among themselves. The size of neurons in the robust nucleus of the archistriatum (RA) and the lateral magnocellular nucleus ofthe neostriatum (lMAN) were inversely correlated with the distance of the EB pellet to HVC; neurons in RA and lMAN were larger when the EB pellets were closer to HVC. This result suggests that implants near HVC were at or near a site of estrogen action. To our knowledge, this is the first demonstration that localized brain implants of estrogen cause morphological masculinization in any species. 1994 John Wiley & Sons, Inc. 相似文献
113.
We investigated the role of the Ras/extracellular-regulated kinase (ERK) pathway in the development of tolerance to Delta(9)-tetrahydrocannabinol (THC)-induced reduction in spontaneous locomotor activity by a genetic (Ras-specific guanine nucleotide exchange factor (Ras-GRF1) knock-out mice) and pharmacological approach. Pre-treatment of wild-type mice with SL327 (50 mg/kg i.p.), a specific inhibitor of mitogen-activated protein kinase kinase (MEK), the upstream kinase of ERK, fully prevented the development of tolerance to THC-induced hypolocomotion. We investigated the impact of the inhibition of ERK activation on the biological processes involved in cannabinoid tolerance (receptor down-regulation and desensitization), by autoradiographic cannabinoid CB1 receptor and cannabinoid-stimulated [(35)S]GTPgammaS binding studies in subchronically treated mice (THC, 10 mg/kg s.c., twice a day for 5 days). In the caudate putamen and cerebellum of Ras-GRF1 knock-out mice and SL327 pre-treated wild-type mice, CB1 receptor down-regulation and desensitization did not occur, suggesting that ERK activation might account for CB1 receptor plasticity involved in the development of tolerance to THC hypolocomotor effect. In contrast, the hippocampus and prefrontal cortex showed CB1 receptor adaptations regardless of the genetic or pharmacological inhibition of the ERK pathway, suggesting regional variability in the cellular events underlying the altered CB1 receptor function. These findings suggest that at least in the caudate putamen and cerebellum, the Ras/ERK pathway is essential for triggering the alteration in CB1 receptor function responsible for tolerance to THC-induced hypomotility. 相似文献
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Greta Eklund Stefan Lang Johan Glindre ?sa Ehlén Maria Alvarado-Kristensson 《The Journal of biological chemistry》2014,289(31):21360-21373
γ-Tubulin is an important cell division regulator that arranges microtubule assembly and mitotic spindle formation. Cytosolic γ-tubulin nucleates α- and β-tubulin in a growing microtubule by forming the ring-shaped protein complex γTuRC. Nuclear γ-tubulin also regulates S-phase progression by moderating the activities of E2 promoter-binding factors. The mechanism that regulates localization of γ-tubulin is currently unknown. Here, we demonstrate that the human Ser/Thr kinase SadB short localizes to chromatin and centrosomes. We found that SadB-mediated phosphorylation of γ-tubulin on Ser385 formed chromatin-associated γ-tubulin complexes that moderate gene expression. In this way, the C-terminal region of γ-tubulin regulates S-phase progression. In addition, chromatin levels of γ-tubulin were decreased by the reduction of SadB levels or expression of a non-phosphorylatable Ala385-γ-tubulin but were enhanced by expression of SadB, wild-type γ-tubulin, or a phosphomimetic Asp385-γ-tubulin mutant. Our results demonstrate that SadB kinases regulate the cellular localization of γ-tubulin and thereby control S-phase progression. 相似文献
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Background
There is a lack of recent studies examining recording of influenza-like illness (ILI) in primary care in the UK over time and according to population characteristics. Our aim was to determine time trends and socio-demographic patterns of ILI recorded consultations in primary care.Methods
We used The Health Improvement Network (THIN) UK primary care database and extracted data on all ILI consultations between 1995 and 2013. We estimated ILI recorded consultation rates per 100,000 person-weeks (pw) by age, gender, deprivation and winter season. Negative binomial regression models were used to examine time trends and the effect of socio-demographic characteristics. Trends in ILI recorded consultations were compared to trends in consultations with less specific symptoms (cough or fever) recorded.Results
The study involved 7,682,908 individuals in 542 general practices. The ILI consultation rate decreased from 32.5/100,000 pw (95% confidence interval (CI) 32.1, 32.9) in 1995–98 to 15.5/100,000 pw (95% CI 15.4, 15.7) by 2010–13. The decrease occurred prior to 2002/3, and rates have remained largely stable since then. Declines were evident in all age groups. In comparison, cough or fever consultation rates increased from 169.4/100,000 pw (95% CI 168.6, 170.3) in 1995–98 to 237.7/100,000 pw (95% CI 237.2, 238.2) in 2010–13. ILI consultation rates were highest among individuals aged 15–44 years, higher in women than men, and in individuals from deprived areas.Conclusion
There is substantial variation in ILI recorded consultations over time and by population socio-demographic characteristics, most likely reflecting changing recording behaviour by GPs. These results highlight the difficulties in using coded information from electronic primary care records to measure the severity of influenza epidemics across time and assess the relative burden of ILI in different population subgroups. 相似文献120.
Chung-Jung Lin Greta S. P. Mok Mang-Fen Tsai Wei-Ta Tsai Bang-Hung Yang Chun-Yuan Tu Tung-Hsin Wu 《PloS one》2015,10(6)