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101.
102.
Non-small-cell lung carcinoma (NSCLC) accounts for approximately 80% of lung cancers with a high metastatic potential. Elucidating the mechanism of NSCLC metastasis will provide new promising targets for NSCLC therapy and benefit its prognosis. Plasmacytoma variant translocation 1 (PVT1) has been proven to be overexpressed in NSCLC. Although the oncogenic role of PVT1 in NSCLC has been reported, its mechanism remains unclear. Here, we verified that the knockdown of PVT1 inhibited NSCLC cell migration and invasion, and that its inhibitory role on A549 cells and H1299 cells was antagonized by interleukin-6 (IL-6) treatment. The results revealed that PVT1 regulates IL-6 by sponging miR-760 and identified the binding site of miR-760 in the 3′-UTR of IL-6. In conclusion, a new mechanism was revealed, wherein PVT1 regulates NSCLC cell migration and invasion via miR-760/IL-6, suggesting PVT1/miR-760/IL-6 as promising prognostic biomarkers and therapeutic targets for NSCLC metastasis. 相似文献
103.
Wei-Hua Song Xiao-Jun Feng Shao-Juan Gong Jian-Ming Chen Shou-Mei Wang Dong-Juan Xing Ming-Hua Zhu Shu-Hui Zhang Ai-Min Xu 《Cancer biology & therapy》2015,16(12):1754-1763
microRNAs (miRNAs) are important regulators of tumor development and progression. In this study, we aimed to explore the expression and role of miR-622 in hepatocellular carcinoma (HCC). We found that miR-622 was significantly downregulated in human HCC specimens compared to adjacent noncancerous liver tissues. miR-622 downregulation was significantly associated with aggressive parameters and poor prognosis in HCC. Enforced expression of miR-622 significantly decreased the proliferation and colony formation and induced apoptosis of HCC cells. In vivo studies demonstrated that miR-622 overexpression retarded the growth of HCC xenograft tumors. Bioinformatic analysis and luciferase reporter assays revealed that miR-622 directly targeted the 3′-untranslated region (UTR) of mitogen-activated protein 4 kinase 4 (MAP4K4) mRNA. Ectopic expression of miR-622 led to a significant reduction of MAP4K4 expression in HCC cells and xenograft tumors. Overexpression of MAP4K4 partially restored cell proliferation and colony formation and reversed the induction of apoptosis in miR-622-overexpressing HCC cells. Inhibition of JNK and NF-κB signaling phenocopied the anticancer effects of miR-622 on HCC cells. Taken together, miR-622 acts as a tumor suppressor in HCC and restoration of miR-622 may provide therapeutic benefits in the treatment of HCC. 相似文献
104.
Xiaoyong Huang Samira Taeb Sahar Jahangiri Elina Korpela Ivan Cadonic Nancy Yu Sergey N. Krylov Emmanouil Fokas Paul C. Boutros Stanley K. Liu 《Oncotarget》2015,6(26):22439-22451
MicroRNA contribute to tumor radiation resistance, which is an important clinical problem, and thus we are interested in identifying and characterizing their function. We demonstrate that miR-620 contributes to radiation resistance in cancer cells by increasing proliferation, and decreasing the G2/M block. We identify the hydroxyprostaglandin dehydrogenase 15-(nicotinamide adenine dinucleotide) (HPGD/15-PGDH) tumor suppressor gene as a direct miR-620 target, which results in increased prostaglandin E2 (PGE2) levels. Furthermore, we show that siRNA targeting of HPGD or administration of exogenous PGE2 recapitulates radioresistance. Targeting of the EP2 receptor that responds to PGE2 using pharmacological or genetic approaches, abrogates radioresistance. Tumor xenograft experiments confirm that miR-620 increases proliferation and tumor radioresistance in vivo. Regulation of PGE2 levels via targeting of HPGD by miR-620 is an innovative manner by which a microRNA can induce radiation resistance. 相似文献
105.
Albert Ferro 《British journal of clinical pharmacology》2015,79(3):351-353
Paracetamol (acetaminophen) overdose is one of the most common causes of acute liver injury in the Western world. To improve patient care and reduce pressure on already stretched health care providers new biomarkers are needed that identify or exclude liver injury soon after an overdose of paracetamol is ingested. This review highlights the current state of paracetamol poisoning management and how novel biomarkers could improve patient care and save healthcare providers money. Based on the widely used concept of defining a target product profile, a target biomarker profile is proposed that identifies desirable and acceptable key properties for a biomarker in development to enable the improved treatment of this patient population. The current biomarker candidates, with improved hepatic specificity and based on the fundamental mechanistic basis of paracetamol-induced liver injury, are reviewed and their performance compared with our target profile. 相似文献
106.
目的 评价哈尔滨市农村癫痫患者健康相关生命质量并分析其影响因素。方法 通过简单随机抽样方法,随机选取哈尔滨市236例惊厥型癫痫患者,基于中国人群的EQ-5D效应值积分体系计算癫痫患者健康效应值,采用秩和检验和Tobit回归模型方法对癫痫患者健康水平影响因素进行分析。结果 调查的236名癫痫患者在5个维度有困难者占比排序为:焦虑或沮丧(42.74%)、疼痛或不适(30.77%)、日常活动(28.63%)、自己照顾自己(18.80%)、行动(16.67%),基于中国积分体系计算癫痫患者健康效应值为0.85,Tobit回归模型结果表明,职业(95%CI = 0.004~0.313,P = 0.045)、体育运动(95%CI = 0.001~0.438,P = 0.049)、最近一次发作时间(95%CI = - 0.316~- 0.020,P = 0.027)、总病程(95%CI = - 0.051~- 0.387,P = 0.011)对癫痫患者的健康效用值得分有统计学差异。结论 癫痫对患者心理方面的影响程度大于生理方面,应加大对癫痫患者心理方面的关注。脑力劳动者、体育运动的癫痫患者健康效用值相对较高,发作时间在0~3个月内、总病程较长的癫痫患者健康效用值相对较低。 相似文献
107.
目的 明确miR-218在胶质瘤组织中的表达,探讨其对胶质瘤血管生成的作用及机制。方法 采用荧光实时定量PCR法和免疫印迹法检测胶质瘤组织和细胞中miR-218、P70核糖体S6激酶1(p70s6k1)的表达情况,采用基质胶塞实验和小管形成实验分别在体内外检测miR-218对新血管生成的影响。结果 21例胶质瘤组织标本中miR-218表达较7例癌旁组织标本明显下调,且表达量与WHO分级有关。过表达miR-218能显著抑制血管生成。MiR-218直接靶向p70s6k1。过表达p70s6k1能部分逆转miR-218对血管新生的抑制作用。结论 MiR-218能通过靶向p70s6k1的表达调控胶质瘤血管生成,进而影响胶质瘤的进展。 相似文献
108.
背景与目的:在前列腺癌标准化疗方案中,多西他赛(docetaxel,DTX)引起的化疗耐药是引起患者死亡的重要原因之一,然而DTX引起的化疗耐药相关机制尚未知。探讨前列腺癌DTX耐药的作用机制。方法:收集2016年6月—2019年6月在武汉市第三医院进行化疗的40例患者,包括20例DTX耐药和20例DTX敏感患者。人前列腺癌细胞系PC-3在一系列逐渐增加的DTX浓度梯度处理下形成耐药株PC-3/DTX。采用实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction,RTFQ-PCR)检测miR-503和TLR4 mRNA的表达,采用蛋白质印迹法(Western blot)检测TLR4蛋白的水平,采用双荧光素酶报告基因检测miR-503和TLR4的相互作用,采用四甲基偶氮唑蓝(methyl thiazolyl tetrazolium,MTT)法检测细胞活力,采用流式细胞术检测细胞凋亡。结果:前列腺癌耐药患者组织和耐药细胞系中miR-503的表达较敏感组显著降低(P=0.013),而TLR4显著增加(P=0.005 6)。过表达miR-503显著抑制耐药细胞的增殖,促进凋亡,同时抑制耐药相关蛋白MDR-1的表达,而过表达TLR4则促进细胞的增殖,抑制凋亡,促进耐药相关蛋白MDR-1的表达。结论:miR-503通过靶向调控TLR4的表达影响前列腺癌的DTX耐药。 相似文献
109.
目的:分析miR-99a对帕金森病细胞模型作用。方法:采用Western blotting以及Real-time PCR方法,对miR-99a以及其靶基因FZD5表达水平进行研究。采用CCK-8方法,检测细胞存活力。结果:过表达miR-99a,可将MPP+抑制PC12细胞存活作用明显缓解,该作用是通过调控miR-99a/FZD5轴完成的。结论:miR-99a在帕金森病细胞模型中,可对MPP+导致的PC12细胞存活抑制作用明显缓解,是通过靶向及下调FZD5实现的。 相似文献
110.