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Neurally selected embryonic stem cells induce tumor formation after long-term survival following engraftment into the subretinal space 总被引:12,自引:0,他引:12
Arnhold S Klein H Semkova I Addicks K Schraermeyer U 《Investigative ophthalmology & visual science》2004,45(12):4251-4255
PURPOSE: To determine whether transplantation of embryonic stem (ES) cells into the subretinal space of rhodopsin-knockout mice has a tumorigenic effect. METHODS: Mouse ES-cell-derived neural precursor cells carrying the sequence for the green fluorescent protein (GFP) gene were grafted subretinally into the eyes of rhodopsin(-/-) mice, whereas control animals underwent sham surgery. Eyes were retrieved after 2, 4, and 8 weeks after cell injection or sham surgery for histologic analysis. RESULTS: Gross morphologic, histologic, and immunohistochemical analysis of eyes at 2 and 4 weeks after engraftment exhibited no morphologic alterations, whereas neoplasia formation was detected in 50% of the eyes evaluated at 8 weeks after engraftment. Because the neoplasias expressed differentiation characteristics of the different germ layers, they were considered to be teratomas. The resultant tumor formation affected almost all layers of the eye, including the retina, the vitreous, and the choroid. CONCLUSIONS: Although ES cells may provide treatment for degenerative disease in the future, their unlimited self-renewal and high differentiation potential poses the risk of tumor induction after engraftment. Thus, more care must be taken before using ES cell transplantation as a therapeutic option for patients with degenerative disease. 相似文献
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Giacaglia LR Mendonca BB Madureira G Melo KF Suslik CA Arnhold IJ Bachega TA 《Journal of pediatric endocrinology & metabolism : JPEM》2001,14(4):415-419
Adrenal nodules have been described in patients with 21-hydroxylase deficiency (21OHD). These nodules are usually considered to be ACTH-dependent, as is the commonly seen diffuse cortical hyperplasia. We evaluated the presence and behavior of adrenal nodules in patients with 21OHD. Based upon hormonal status and treatment compliance, the patients were classified into three categories: poor, regular and good control. Out of the 26 patients, eight had the non-classic, four salt-wasting and 14 simple virilizing forms. All patients underwent initial adrenal morphological studies, either by CT or MRI. Those with nodules were reevaluated after 12 months of adequate replacement therapy. Nodules were found in four of eight untreated patients and two of three patients with poor hormonal control, but not in the 15 patients with regular or good control. Adrenal nodules in these six patients demonstrated a considerable size reduction and even disappearance after adequate replacement therapy, showing that these nodules were ACTH-dependent. Thus, six out of 26 patients with 21OHD presented adrenal nodules, which were more frequent in the untreated or poorly-controlled patients, and all regressed in size after adequate therapy. 相似文献
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Schumacher A Arnhold S Addicks K Doerfler W 《Molecular and cellular neurosciences》2003,23(4):669-680
Staurosporine (STS), a broad spectrum protein kinase inhibitor, was previously shown to induce neurite outgrowth in several neuroblastoma cell lines. However, data on the neurotrophic potential of this alkaloid in embryonic stem cell systems were not available. Therefore, three mouse ES cell lines, IB10, RW4, and Bruce 4, were induced to enter neurogenesis in culture at low concentrations of STS. These cells differentiated into epidermal growth factor-responsive neural precursor cells, formed neurospheres, and further developed to neurons and astrocytes. The clonally derived neurospheres consisted of multipotent cells which exhibited some of the classical characteristics of early CNS stem cells and could be propagated in vitro. STS was antagonistic in several ways to retinoic acid (RA), a vitamin A metabolite, which promotes neuritogenesis. Results from RT-PCR experiments and inhibition studies with RA provided evidence that staurosporine exerted its neurotrophic effects through the induction of very late levels of the nerve growth factor and protein kinase C neurogenesis pathways. 相似文献
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Mike Arnhold Yanina Dening Michaël Chopin Esteban Arévalo Mathias Schwarz Heinz Reichmann Gabriele Gille Richard H. W. Funk Francisco Pan-Montojo 《Clinical autonomic research》2016,26(3):211-222
Introduction
Involvement of the peripheral nervous system (PNS) is relatively common in Parkinson’s disease (PD) patients. PNS alterations appear early in the course of the disease and are responsible for some of the non-motor symptoms observed in PD patients. In previous studies, we have shown that environmental toxins can trigger the disease by acting on the enteric nervous system.Material and methods
Here, we analyzed the effect of mitochondrial Complex I inhibition on sympathetic neuritis in vivo and sympathetic neurons in vitro. Combining in vivo imaging and protein expression profiling.Results
we found that rotenone, a widely used mitochondrial Complex I inhibitor decreases the density of sympathetic neurites innervating the gut in vivo, while in vitro, it induces the redistribution of intracellular alpha-synuclein and neurite degeneration. Interestingly, sympathetic neurons are much more resistant to rotenone exposure than mesencephalic dopaminergic neurons.Conclusion
Altogether, these results suggest that enteric sympathetic denervation could be an initial pre-motor alteration in PD progression that could be used as an early biomarker of the disease.40.
Adolfo JO Scherr Joao Paulo SN Lima Emma C Sasse Carmen SP Lima André D Sasse 《BMC cancer》2011,11(1):115