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1.
This commentary focuses on the emerging intersection between BMP/TGF-β signaling roles in nervous system function and the amyotrophic lateral sclerosis (ALS) disease state. Future research is critical to elucidate the molecular underpinnings of this intersection of the cellular processes disrupted in ALS and those influenced by BMP/TGF-β signaling, including synapse structure, neurotransmission, plasticity, and neuroinflammation. Such knowledge promises to inform us of ideal entry points for the targeted modulation of dysfunctional cellular processes in an effort to abrogate ALS pathologies. It is likely that different interventions are required, either at discrete points in disease progression, or across multiple dysfunctional processes which together lead to motor neuron degeneration and death. We discuss the challenging, but intriguing idea that modulation of the pleiotropic nature of BMP/TGF-β signaling could be advantageous, as a way to simultaneously treat defects in more than one cell process across different forms of ALS. 相似文献
2.
Chrystalle Katte Carreon Annachiara Benini Christopher Baird David Hoganson Michele Borisuk Sitaram Emani Sophie Hofferberth Robert F. Padera Stephen P. Sanders 《The Journal of thoracic and cardiovascular surgery》2019,157(1):342-350.e3
Objectives
Although valved venous homografts (VVHs) are used for establishing right ventricle-to-pulmonary artery continuity in some complex heart defects, the tissue changes that occur in situ have not been described. We review the gross and microscopic changes observed in explanted VVH conduits and their effects on functionality.Methods
In total, 20 explanted VVH conduits were evaluated for valve integrity, presence of thrombus, and stenosis. Hematoxylin and eosin– and trichrome-stained sections were reviewed for neointima formation, wall remodeling, inflammation, and calcification. Regurgitation and narrowing were assessed on pre-explant echocardiogram, and angiographic video clips were correlated with tissue findings. The source of the proliferating cells within the conduits was investigated by fluorescent in situ hybridization.Results
Thirteen male and 7 female infants underwent VVH implantation either as part of a composite Sano shunt (65%) or to establish right ventricle-to-pulmonary artery continuity in biventricular hearts (35%). The median duration of conduits in situ was 140 days (range: 98-340 days). Conduits were predominantly explanted for staged conversion to bidirectional Glenn (60%) and conduit upsizing (20%). The valves remained intact and functional in 75% of cases. Occlusive thrombosis was absent in all. Wall thickening due to neointima formation and wall remodeling was uniformly present and appeared to be driven by smooth muscle actin–expressing cells, which by fluorescent in situ hybridization are predominantly of recipient origin. Minimal calcification and mild adventitial chronic inflammation were present.Conclusions
Vein wall thickening is a uniform finding and can cause stenosis. The valves remain functional in most, and vein walls undergo remodeling with only minimal inflammation and calcification. 相似文献3.
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Ermei Lu Qian Wang Shengcun Li Caiming Chen Weibo Wu Yang Xin Zi Xu Peng Zhou Wenzhan Tu Xinfa Lou Gaofeng Rao Guanhu Yang Songhe Jiang Kecheng Zhou 《Journal of neuroscience research》2020,98(6):1198-1212
Microglial polarization to the anti-inflammatory M2 phenotype is essential in resolving neuroinflammation, making it a promising therapeutic strategy for stroke intervention. The actin cytoskeleton is known to be important for the physiological functions of microglia, including migration and phagocytosis. Profilin 1 (PFN1), an actin-binding protein, is involved in the dynamic transformation and reorganization of actin. However, the role of PFN1 in microglial polarization and ischemia/reperfusion injury is unclear. The role of PFN1 on microglial polarization was examined in vitro in BV2 microglial cells subjected to oxygen-glucose deprivation/reoxygenation (OGDR) and in vivo in male mice after transient middle cerebral artery occlusion (MCAO). Knockdown of PFN1 inhibited M1 microglial polarization and promoted M2 microglia polarization 48 hr after OGDR stimulation in BV2 cells and 7 days after MCAO-induced injury in male mice. RhoA/ROCK pathway was involved in the regulation of PFN1 during microglial polarization. Knockdown of PFN1 also significantly attenuated brain infarcts and edema, improved cerebral blood flow and neurological deficits in MCAO-injured mice. Inhibition of PFN1 effectively protected the brain against ischemia/reperfusion injuries by promoting M2 microglial polarization in vitro and in vivo. 相似文献
6.
Ochratoxin A (OTA) is a mycotoxin that mainly causes nephrotoxicity. The single nephrotoxicity of OTA exposure on glomeruli or renal tubule had been well documented, however, the comparison toxicity between it is still unclear. Here, C57BL/6 mice and two types of nephrocyte were treated with concentration-gradient OTA to explore its differentiation nephrotoxicity. Results showed that OTA induced nephrotoxicity in vivo and in vitro, manifested as the deteriorative kidney function in mice and the cut-down cell viability in nephrocyte. Besides, results of murine kidney pathological section and IC50 of two types nephrocyte indicated that OTA-induced toxicity in renal tubule was higher than its in glomeruli. In addition, OTA exposure induced autophagy signaling differentiation expression. It revealed that autophagy was implicated in OTA-induced differential nephrotoxicity in glomeruli and renal tubule. Altogether, we proved that OTA induces a differentiation nephrotoxicity in glomeruli and renal tubule, and it is related to autophagy differential regulation. 相似文献
7.
目的 分析长链非编码RNA(lncRNA)肌动蛋白纤维相关蛋白1-反义RNA1(AFAP1-AS1)在口腔鳞状细胞癌(OSCC)中的表达及其对OSCC细胞生物行为学的影响,初步探讨其可能的作用机制。方法 采用实时荧光定量聚合酶链反应(qRT-PCR)检测OSCC患者(55例)癌组织、癌旁正常黏膜组织及人口腔鳞状细胞癌SCC25、人正常口腔角质细胞株(NOK)细胞中lncRNA AFAP1-AS1的表达,分析AFAP1-AS1与OSCC患者病理特征的相关性,通过Kaplan-Meier生存曲线分析AFAP1-AS1与患者预后的关系。AFAP1-AS1 siRNA转染SCC25细胞,细胞计数(CCK-8)及Transwell实验分别检测细胞增殖、迁移和侵袭的变化,蛋白质印迹(Western blot)检测侵袭相关蛋白、肌动蛋白纤维相关蛋白1(AFAP1)及Rho GTP酶家族成员蛋白的表达情况,免疫荧光染色检测细胞骨架肌动蛋白微丝结构的变化。结果 OSCC组织中AFAP1-AS1的表达高于癌旁正常黏膜组织,SCC25细胞中AFAP1-AS1的表达高于NOK细胞(P<0.001)。AFAP1-AS1的表达与OSCC的分化程度、TNM分期及淋巴结转移密切相关(P<0.05),AFAP1-AS1高表达患者的生存率低于AFAP1-AS1低表达者(P<0.05)。AFAP1-AS1 siRNA转染后AFAP1-AS1的表达水平下调,SCC25细胞的增殖、迁移和侵袭能力降低,AFAP1、RhoA、Rac2、Rab10、RhoGDI和Pfn1的表达上调,RhoC的表达下调,细胞骨架中应力纤维丝减少,肌动蛋白完整性丢失。结论 lncRNA AFAP1-AS1在OSCC组织及SCC25细胞中高表达,与OSCC的发生进展及预后相关。下调AFAP1-AS1能够抑制OSCC的增殖、迁移和侵袭能力,其可能是通过调控肌动蛋白纤维丝的完整性实现的。 相似文献
8.
茵陈五苓散对动脉粥样硬化大鼠肌动蛋白表达的影响 总被引:1,自引:0,他引:1
目的观察茵陈五苓散对动脉粥样硬化(AS)大鼠血管平滑肌细胞(VSMC)肌动蛋白表达的影响。方法70只Wistar大鼠随机分为正常组、模型组、茵陈五苓散组、胶股蓝组。采用高脂饲料喂饲法复制大鼠动脉粥样硬化模型,造模1个月后抽样检测大鼠主动脉,以发现动脉粥样硬化斑块为造模成功指标。治疗1个月后分别检测血脂、血液流变学,用HE染色观察主动脉组织学变化,用透射电镜观察大鼠主动脉组织超微结构变化,用免疫组化法观察大鼠主动脉VSMC肌动蛋白的变化。结果茵陈五苓散对动AS模型大鼠有明显的降脂作用,能改善血液流变性、消退斑块、维持主动脉组织结构及功能,使细胞肌动蛋白表达趋于正常。结论茵陈五苓散具有良好的抗AS作用,它可能是通过调整细胞肌动蛋白的表达来实现的。 相似文献
9.
Requirement of the F‐actin‐binding activity of l‐afadin for enhancing the formation of adherens and tight junctions 下载免费PDF全文
Shotaro Sakakibara Tomohiko Maruo Muneaki Miyata Kiyohito Mizutani Yoshimi Takai 《Genes to cells : devoted to molecular & cellular mechanisms》2018,23(3):185-199
The apical junctional complex consists of adherens junctions (AJs) and tight junctions (TJs) in polarized epithelial cells, which are attached to each other to form a sheet. Actin filaments (F‐actin) are associated with AJs and TJs and required for the formation and maintenance of this complex. l‐Afadin is an F‐actin‐binding protein, which is localized at AJs through binding to the cell adhesion molecule nectin, and regulates the formation of AJs and TJs. However, the role of the F‐actin‐binding activity of l‐afadin for the formation of the apical junctional complex remains unknown. We generated here the cultured EpH4 mouse mammary epithelial cells in which afadin was genetically ablated. In the Ca2+ switch assay, the formation of both AJs and TJs was markedly impaired in the afadin‐deficient cells. Re‐expression of l‐afadin in the afadin‐deficient cells fully restored the formation of both AJs and TJs, but the re‐expression of the l‐afadin mutant lacking the FAB domain did not completely restore the formation of AJs or TJs. These results indicate that the F‐actin‐binding activity of l‐afadin is required for enhancing the formation of both AJs and TJs. 相似文献
10.