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1.
《Molecular therapy》2022,30(3):1171-1187
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2.
目的通过研究诱骗受体2(DcR2)在小鼠胚肾发育过程中的定位和表达,探讨DcR2在胚肾发育中与细胞衰老的关系。 方法分别选取胚龄为12.5 d、16.5 d、20.5 d和出生后8w小鼠的肾脏组织,使用过碘酸雪夫(PAS)染色观察肾组织形态,定量RT-PCR检测肾组织DcR2 mRNA表达水平,免疫组织化学染色观察DcR2的表达分布,免疫荧光共染检测DcR2与近端肾小管标志绒毛蛋白villin、远端肾小管标志水通道蛋白2(AQP-2)、衰老标志P16、胞核形态标志物核纤层蛋白B1(LaminB1)、增殖标志Ki-67和增殖细胞核抗原(PCNA)的共表达关系。 结果随着胚肾的发育,胚肾组织中DcR2 mRNA及蛋白表达逐渐增多,且明显高于成年肾脏;DcR2特异性表达于肾小管,且与villin共表达,但不与AQP-2共表达;DcR2阳性细胞高表达P16,却低表达LaminB1、Ki-67和PCNA。 结论DcR2特异性表达于胚肾近端肾小管细胞,且表达水平随胚龄增长而增多。此外,DcR2阳性细胞具有衰老相关表型,提示DcR2可能在胚肾发育过程中通过调控细胞衰老而具有重要作用。  相似文献   
3.
Skin is the largest organ of the body with important protective functions, which become compromised with time due to both intrinsic and extrinsic ageing processes. Cellular senescence is the primary ageing process at cell level, associated with loss of proliferative capacity, mitochondrial dysfunction and significantly altered patterns of expression and secretion of bioactive molecules. Intervention experiments have proven cell senescence as a relevant cause of ageing in many organs. In case of skin, accumulation of senescence in all major compartments with ageing is well documented and might be responsible for most, if not all, the molecular changes observed during ageing. Incorporation of senescent cells into in-vitro skin models (specifically 3D full thickness models) recapitulates changes typically associated with skin ageing. However, crucial evidence is still missing. A beneficial effect of senescent cell ablation on skin ageing has so far only been shown following rather unspecific interventions or in transgenic mouse models. We conclude that evidence for cellular senescence as a relevant cause of intrinsic skin ageing is highly suggestive but not yet completely conclusive.  相似文献   
4.
目的:观察人参-三七-川芎提取物对延缓内皮微粒(EMPs)诱导的血管内皮细胞衰老的影响,并探索其作用机制。方法:以人脐静脉内皮细胞(HUVECs)为研究对象,复制性衰老10~12代细胞作为衰老模型,实验分为年轻组(2~4代细胞)、衰老组(10~12代细胞)、单纯EMPs干预组(提取衰老细胞产生的EMPs来干预年轻细胞)以及中药低、中、高剂量组(200,300,400 mg·L-1)。结合衰老相关β半乳糖苷酶(SA-β-gal)染色法和碘化丙啶(PI)单染法检测细胞周期来判断细胞衰老程度。采用细胞活性和细胞增殖检测(CCK-8)法筛选给药浓度,两步离心法分离出EMPs,藻红蛋白(PE)CD31抗体或异硫氰酸荧光素(FITC)Annexin V标记分离得到的EMPs,并用流式细胞术进行定量,2’,7’-二氯荧光素二乙酸酯(DCFDA)染色检测细胞内活性氧(ROS)水平。结果:与衰老组比较,中药给药组可显著降低衰老细胞SA-β-gal活性(P<0.01),使细胞周期S期阻滞得到恢复(P<0.01),并降低衰老细胞分泌CD31+EMPs及Annexin V+EMPs的数量(P<0.05)。与年轻组比较,单纯EMPs干预组可诱导年轻细胞SA-β-gal活性增强(P<0.01),细胞周期阻滞于S期(P<0.05),与衰老组比较,但在EMPs干预的同时给予中药干预后,可明显抑制EMPs介导增强的SA-β-gal活性(P<0.05),并使S期阻滞得到恢复。中药组还可明显抑制EMPs诱导的细胞内ROS增高(P<0.05,P<0.01)。结论:人参-三七-川芎提取物可通过影响EMPs延缓复制性血管内皮细胞衰老,其机制可能与抑制EMPs诱导的细胞内ROS水平增高有关。  相似文献   
5.
The abnormal expressions of microRNAs (miRNAs) are known to be associated with various pathophysiological processes that lead to the development of a plethora of diseases including cancer. Among several miRNAs studied so far, miR‐197 has been reported to play a vital role either as an oncogene or tumor suppressor in different cancers. However, its role in carcinogenesis of fibrosarcoma has not yet been elucidated. Therefore, the current study investigated the role of miR‐197‐5p, which is significantly downregulated in HT1080 fibrosarcoma cells compared to IMR90‐tert fibroblast cells. The transient overexpression of miR‐197‐5p causes a significant decrease in viability and proliferation of fibrosarcoma cells in both concentration‐ and time‐dependent manners. Interestingly, we did not observe any significant changes in cell cycle pattern or apoptotic cell populations, but rather noticed cellular senescence of fibrosarcoma cells upon overexpression of miR‐197‐5p. Further, this miRNA suppresses the metastatic properties, such as migration, invasion, and anchorage‐independent growth of fibrosarcoma possibly through targeting KIAA0101, which is a proliferating cell nuclear antigen‐associated factor and overexpressed in the malignancy. In nutshell, our result revealed that miR‐197‐5p acts as an oncosuppressor miRNA in fibrosarcoma through target regulation of KIAA0101, which can be exploited for developing RNA‐based therapeutic strategies for the cure of this malignancy.  相似文献   
6.
Despite advances in cancer therapeutics and the integration of personalized medicine, the development of chemoresistance in many patients remains a significant contributing factor to cancer mortality. Upon treatment with chemotherapeutics, the disruption of homeostasis in cancer cells triggers the adaptive response which has emerged as a key resistance mechanism. In this review, we summarize the mechanistic studies investigating the three major components of the adaptive response, autophagy, endoplasmic reticulum (ER) stress signaling, and senescence, in response to cancer chemotherapy. We will discuss the development of potential cancer therapeutic strategies in the context of these adaptive resistance mechanisms, with the goal of stimulating research that may facilitate the development of effective cancer therapy.  相似文献   
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8.
Immune senescence is associated with age-related diseases (i.e. infectious disease, cardiovascular diseases and cancers). Chronic kidney disease patients die prematurely when compared with general population, because of a higher occurrence of infections, cardiovascular events and cancer. These diseases are commonly observed in the elderly population and frequently associated with immune senescence. Indeed, chronic kidney disease causes a premature aging of the T lymphocyte compartment, widely related to a decrease in thymic function, a phenomenon that plays a key role in the onset of age-related diseases in chronic kidney disease patients. The degree of immune senescence also influences patients’ outcome after renal transplantation, particularly the risk of acute rejection and infections. Partial reversion of pre-transplant immune senescence is observed for some renal transplant patients. In conclusion, to reduce the increasing incidence of morbidity and mortality of chronic kidney disease patients, a better knowledge of uremia-induced immune senescence would help to pave the way to build clinical studies and promote innovative therapeutic approaches. We believe that therapeutic reversion and immune senescence prevention approaches will be part of the management of chronic kidney disease patients in the future.  相似文献   
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10.
目的探讨骨肉瘤细胞(OS)能否脱逸化疗至细胞衰老和再增殖;评价逃逸衰老的细胞成瘤能力,从新的角度解释骨肉瘤复发的机制。方法多柔比星(DOX)诱导骨肉瘤细胞U2OS和MG63制备衰老的细胞模型,SA-Gal染色法检测细胞衰老;Western blot检测衰老相关分子。更换成不含DOX的培养基培养75 d,细胞计数检测细胞增殖和计算脱逸率。而后分为3组:对照组、衰老细胞组和脱逸衰老细胞组,琼脂糖克隆实验检测集落形成和裸鼠成瘤实验检测成瘤能力。结果超过90%的U2OS和MG63呈SA-Gal染色阳性;衰老相关的细胞分子p-p53、p-Rb和p-γH2AX明显升高(P<0.05)。75 d后,观察到有细胞重新增殖(脱逸率百万分之一),具有集落形成和裸鼠成瘤能力。结论衰老的骨肉瘤细胞能够脱逸细胞衰老状态重新增殖并具有成瘤能力。  相似文献   
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