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1.

Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

Objectives

To investigate the molecular mechanism by which botulinum toxin improves rosacea lesions.

Methods

Primary human and murine mast cells were pretreated with onabotulinum toxin A or B or control. Mast cell degranulation was evaluated by β-hexosaminidase activity. Expression of botulinum toxin receptor Sv2 was measured by qPCR. The presence of SNAP-25 and VAMP2 was established by immunofluorescence. In vivo rosacea model was established by intradermally injecting LL-37 with or without onabotulinum toxin A pretreatment. Mast cell degranulation was assessed in vivo by histologic counts. Rosacea biomarkers were analyzed by qPCR of mouse skin sections.

Results

Onabotulinum toxin A and B inhibited compound 48/80-induced degranulation of both human and murine mast cells. Expression of Sv2 was established in mouse mast cells. Onabotulinum toxin A and B increased cleaved SNAP-25 and decreased VAMP2 staining in mast cells respectively. In mice, injection of onabotulinum toxin A significantly reduced LL-37-induced skin erythema, mast cell degranulation, and mRNA expression of rosacea biomarkers.

Conclusions

These findings suggest that onabotulinum toxin reduces rosacea-associated skin inflammation by directly inhibiting mast cell degranulation. Periodic applications of onabotulinum toxin may be an effective therapy for refractory rosacea and deserves further study.  相似文献   
2.
The in situ thermal protein denaturation and its correlation with direct hyperthermic cell injury in Dunning AT-1 prostate tumor cells were investigated in this study. The in situ thermal protein denaturation was studied using both Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The FTIR spectra at different temperatures show changes in protein secondary structure (from alpha helix to extended beta sheet) during in situ thermal protein denaturation within AT-1 cells. Calorimetric studies using DSC show that endothermic heat release is associated with the in situ thermal protein denaturation. Furthermore, both the secondary structure changes detected by FTIR and the calorimetric changes detected by DSC were quantified and the kinetics of the overall in situ thermal protein denaturation was derived under different heating conditions. The onset temperature where the overall in situ thermal protein denaturation is first detectable was found to be scanning rate dependent (approximately 41 degrees C at 2 degrees C min(-1) and approximately 44 degrees C at 5 degrees C min(-1)). The kinetics of the overall in situ thermal protein denaturation was derived from both DSC and FTIR measurements and was fit using kinetic and statistical models. The kinetic data determined by FTIR and DSC under the same heating conditions match well with each other. The activation energy of the overall in situ thermal protein denaturation is found to be strongly dependent on the temperature range considered (the activation energy ranges from approximately 110 kJ mol(-1) between 44 and 90 degrees C to approximately 750 kJ mol(-1) between 44 and 50 degrees C). However, its dependence on heating rate is negligible. Several denaturation peaks, including a dominant one between approximately 62 and 65 degrees C, are identifiable from both the DSC and the FTIR results. To investigate directly the relationship between thermally induced cell injury and the in situ thermal protein denaturation, both acute (propidium iodide dye exclusion, assessed 3-h postthermal treatment) and chronic (clonogenics, assessed 7-day postthermal treatment) cell injury were quantified using AT-1 cells prepared under the same conditions as for the DSC protein studies. Comparisons of the results from the cell injury studies and the DSC protein denaturation studies show that the overall in situ thermal protein denaturation correlates well with both the acute and the chronic cell injury, which suggests that overall in situ thermal protein denaturation is an important mechanism of direct hyperthermic cell injury in AT-1 cells at the macromolecular level.  相似文献   
3.
Transcranial magnetic stimulation   总被引:2,自引:0,他引:2  
We investigated the effects of unilateral cold-water vestibular stimulation on healthy subjects' performance in two cognitive tasks known to be differentially mediated by the two cerebral hemispheres. In a first experiment (right-hemisphere task), subjects memorized object-location associations while being stimulated with cold water in the left ear or right ear or not at all (control group). In the second experiment (left-hemisphere task), subjects memorized a list of sequentially presented function words while being stimulated in the same manner as the subjects in the first experiment. A recall phase followed each encoding phase. In the first experiment, subjects who had been stimulated in the left ear recalled the object locations significantly faster than subjects who had been stimulated in the right ear and those in the control group. The second experiment yielded the reverse pattern: correct word recognition was faster for subjects who had been stimulated in the right ear than for subjects stimulated in the left ear and those of the control group. We suggest that unilateral caloric stimulation leads to a selective activation of contralateral cerebral structures and speeds up cognitive processes mediated by these structures. These results are discussed with respect to findings in neglect patients and functional-imaging studies in healthy subjects.  相似文献   
4.
引入市场机制,采取分权、分级与分类管理等政策与措施是当今国际卫生体制改革中的主流特点,由于各个国家的社会经济体制与卫生保健制度不同,这些改革政策与措施所产生的影响与效果也各具特色.因此,在深化我国卫生体制改革的进程中,借鉴国际卫生体制改革的经验与教训具有一定的现实意义.  相似文献   
5.
骨质疏松症是临床常见病多发病。随着人口老龄化的进展,骨质疏松的患病率逐年增加。目前国内外主要应用药物(包括西药和中药)疗法,其研究开展的较早也较系统,已取得了较大的进展,药理学研究多局限于口服药物和注射药物的研究。近年来,伴随着透皮剂和离子导入等理化技术的发展,中药经皮给药治疗骨质疏松症已取得一定进展。就此方面对补肾药物经皮穴位给药治疗骨质疏松症的机理作一探讨。  相似文献   
6.
~3H前体掺入实验表明国产洋红霉素对L121l细胞DNA合成具有显著的抑制作用,药物作用一小时,IC_(50)为2.47μg/ml。小牛胸腺DNA溶液碱变性、热变性和粘度实验表明洋红霉素可以和DNA结合;紫外光谱位移实验和荧光淬实验进一步证明这种结合。提示国产洋红霉素的抗肿瘤机理可能与药物和DNA结合后,引起DNA分子模板功能障碍有关。  相似文献   
7.
目的:基于网络药理学研究姜天麻对偏头痛的作用机制.方法:选取前期姜制天麻前后已确定的20种差异性成分为研究对象,通过Swiss target prediction等数据库,预测这些成分与偏头痛相关靶点之间关系,利用Cytoscape软件构建"药物-化合物-靶点-疾病"的网络图,并进行GO功能和KEGG通路富集分析.结果...  相似文献   
8.
腰椎牵引的力学机理与生理效应的探讨   总被引:8,自引:0,他引:8  
[目的]探讨腰椎牵引的力学机理与生理效应。[方法]根据本院治疗资料,结合文献进行回顾性分析。[结果]牵引重量为:40kg+体重15%~20%,治疗189例,优良率84.1%。按病程分析:3 a及其以下者优良率90.5%;3 a以上者优良率68.3%。[结论]在重力牵引下,腰骶神经根松弛、位移,偏离了突出髓核的高峰,建立了新的、和谐的“根-盘”关系,压迫或牵引减轻或消失,腰腿痛缓解或痊愈。适宜的牵引重量和正确地体位是提高疗效的关键。  相似文献   
9.
目的 了解深圳市观澜人民医院社区健康服务运行机制改革的做法与成效,为社区健康服务体系建设的可持续发展提供有益的意见和建议.方法 采用现场实验性研究方法进行改革试点,综合评价由第三方完成.结果 观澜人民医院的社区健康服务运行机制改革取得了显著成效,公共卫生服务工作得到较好落实,居民和员工的满意度大幅度提升.结论 通过深入开展社区健康服务运行机制改革,可以保障社区健康服务的可持续发展,应不断创造条件深入推进深圳市社区健康服务运行机制的改革工作.  相似文献   
10.
目的探讨阿维A酸能否诱导原代人皮肤角质形成细胞凋亡及阿维A酸抗银屑病的作用机制。方法采用酶联免疫分析法、流式细胞术双标记法及透射电镜等方法观察药物作用细胞前后凋亡的诱导情况。结果阿维A酸可诱导原代人皮肤角质形成细胞凋亡,细胞凋亡程度呈现明显的浓度及时间依赖性。结论阿维A酸可诱导原代人皮肤角质形成细胞凋亡,阿维A酸治疗银屑病临床疗效肯定。  相似文献   
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