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1.
目的 对比研究朝鲜淫羊藿酸性多糖酯化还原前后的理化特性,并探讨其改善油酸诱导的肝癌HepG2细胞脂质堆积活性的差异。方法 采用高效凝胶渗透色谱法测定朝鲜淫羊藿酸性多糖(EFPA)的均一性和分子量,高效液相色谱法测定EFPA和酯化还原后朝鲜淫羊藿酸性多糖(EFPA-R)的单糖组成;采用油酸(OA)处理HepG2细胞诱导建立脂质蓄积模型,不同浓度EFPA与EFPA-R(10、30、100、300 μg·mL-1)分别和OA共同作用于细胞24 h,采用CCK-8试剂盒测定细胞存活率,油红O染色观察细胞内脂滴蓄积情况,并采用试剂盒测定细胞内总胆固醇(TC)、甘油三酯(TG)含量。结果 EFPA为成分均一的多糖组分,分子量为125.8 kDa,由甘露糖、葡萄糖、半乳糖、葡萄糖醛酸和阿拉伯糖组成,摩尔比为1.7∶7.4∶1.4∶1.8∶1.0,葡萄糖占比最大,EFPA-R由甘露糖、葡萄糖、半乳糖和阿拉伯糖组成,摩尔比为0.8∶10.6∶2.1∶1.0;在10-300 μg·mL-1范围内,EFPA和EFPA-R对HepG2细胞的抑制作用较弱,作为给药浓度;与空白组相比,模型组细胞中TC、TG含量显著升高(P < 0.01),细胞内红色脂滴显著增多,与模型组相比,EFPA可显著降低细胞中TC、TG含量(P < 0.01),明显减少细胞内红色脂滴(P < 0.05或P < 0.01),EFPA-R干预后细胞则无明显变化。结论 EFPA可明显改善HepG2细胞脂质堆积情况,且呈现剂量依赖性,而半乳糖醛酸(GalA)的存在可能是其抑制HepG2细胞脂质蓄积的关键因素。 相似文献
2.
Mette Nissen Tiina‐Mari Ikheimo Jukka Huttunen Ville Leinonen Henna‐Kaisa Jyrkknen Mikael von und zu Fraunberg 《Neuromodulation》2021,24(1):102-111
ObjectiveSpinal cord stimulation (SCS) is an effective treatment in failed back surgery syndrome (FBSS). We studied the effect of preimplantation opioid use on SCS outcome and the effect of SCS on opioid use during a two-year follow-up period.Materials and methodsThe study cohort included 211 consecutive FBSS patients who underwent an SCS trial from January 1997 to March 2014. Participants were divided into groups, which were as follows: 1) SCS trial only (n = 47), 2) successful SCS (implanted and in use throughout the two-year follow-up period, n = 131), and 3) unsuccessful SCS (implanted but later explanted or revised due to inadequate pain relief, n = 29). Patients who underwent explantation for other reasons (n = 4) were excluded. Opioid purchase data from January 1995 to March 2016 were retrieved from national registries.ResultsHigher preimplantation opioid doses associated with unsuccessful SCS (ROC: AUC = 0.66, p = 0.009), with 35 morphine milligram equivalents (MME)/day as the optimal cutoff value. All opioids were discontinued in 23% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.004). Strong opioids were discontinued in 39% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.04). Mean opioid dose escalated from 18 ± 4 MME/day to 36 ± 6 MME/day with successful SCS and from 22 ± 8 MME/day to 82 ± 21 MME/day with unsuccessful SCS (p < 0.001).ConclusionsHigher preimplantation opioid doses were associated with SCS failure, suggesting the need for opioid tapering before implantation. With continuous SCS therapy and no explantation or revision due to inadequate pain relief, 39% of FBSS patients discontinued strong opioids, and 23% discontinued all opioids. This indicates that SCS should be considered before detrimental dose escalation. 相似文献
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4.
Her-Shyong Shiah Nai-Jung Chiang Chia-Chi Lin Chia-Jui Yen Hui-Jen Tsai Shang-Yin Wu Wu-Chou Su Kwang-Yu Chang Ching-Chiung Wang Jang-Yang Chang Li-Tzong Chen 《The oncologist》2021,26(4):e567-e579
Lessons Learned
- SCB01A is a novel microtubule inhibitor with vascular disrupting activity.
- This first‐in‐human study demonstrated SCB01A safety, pharmacokinetics, and preliminary antitumor activity.
- SCB01A is safe and well tolerated in patients with advanced solid malignancies with manageable neurotoxicity.
5.
Zongzhang Huang Qigu Yao Jianping Zhu Ying He Yanghao Chen Feng Wu Teng Hua 《Diagnostic and interventional imaging》2021,102(5):279-285
PurposeThe purpose of this study was to make a systematic review and meta-analysis to determine the stent diameter (8 mm vs. 10 mm) that conveys better safety and clinical efficacy for transjugular intrahepatic portosystemic shunt (TIPS).Materials and methodsFour databases were used to identify clinical trials published from inception until March 2020. Data were extracted to estimate and compare one-year and three-year overall survivals, hepatic encephalopathy, variceal rebleeding, and shunt dysfunction rates between patients with 8 mm covered stents and those with 10 mm covered stents.ResultsFive eligible studies were selected, which included 489 patients (316 men, 173 women). The 8 mm covered stent group had higher efficacy regarding one-year or three-year overall survival (odds ratio [OR], 2.88; P = 0.003) and (OR, 1.81; P = 0.04) and lower hepatic encephalopathy (OR, 0.69; P = 0.04) compared with 10 mm covered stent group. There were no significant differences in variceal rebleeding rate (OR 0.80; P = 0.67). However, shunt dysfunction was lower in 10 mm covered stent group (OR, 2.26; P = 0.003).ConclusionsOur results suggest that the use of 8 mm covered stents should be preferred to that of 10 mm covered stents for TIPS placement when portal pressure is frequently monitored. 相似文献
6.
目的探讨C型凝集素受体Dectin-2在烟曲霉菌感染中的作用及机制。方法用紫外线灭活的烟曲霉菌膨胀态分生孢子刺激野生型(wild type, WT)和Dectin-2缺失(Clec4n-/-)小鼠骨髓来源的巨噬细胞(bone marrow derived macrophages, BMDMs)。刺激20min及40min后,利用Western印迹法检测BMDMs中脾酪氨酸激酶(spleen tyrosine kinase, Syk)和核转录因子κB抑制因子(inhibitor-κB, IκBα)的磷酸化水平。刺激16h后,利用酶联免疫吸附法(enzyme-linked immunosorbent assay, ELISA)检测BMDMs细胞上清液中IL-6、TNF-α和IL-12p40的水平。另一方面,利用压舌感染的方法在WT和Clec4n-/-小鼠中构建烟曲霉菌肺部感染模型。感染2d后,统计小鼠整个肺脏荷菌量,并检测肺脏匀浆液中IL-6和IL-12p40水平。结果体外试验提示,烟曲霉菌刺激后,Dectin-2缺失的BMDMs中Syk和IκBα的磷酸化水平及IL-6、TNF-α和IL-12p40水平显著下降(P<0.05)。体内试验发现,烟曲霉菌感染后,Dectin-2缺失小鼠中肺脏荷菌量显著升高(P<0.05),肺脏匀浆液内IL-6、IL-12p40水平显著降低(P<0.05)。结论C型凝集素受体Dectin-2激活烟曲霉菌诱导的NF-κB信号通路并介导促炎细胞因子的产生,可在小鼠肺烟曲霉菌病动物模型中发挥保护性作用。 相似文献
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8.
目的:探索嘌呤能受体X1(purinergic receptor,P2RX1)与肺腺癌(LUAD)患者预后及免疫细胞浸润的相关性。方法:利用生物信息学技术分析非小细胞肺癌中P2RX1的表达及其甲基化与患者预后的关系,对P2RX1共表达基因进行富集分析并筛选核心基因。利用TIMER 2.0数据库、R软件等分析P2RX1与免疫细胞、免疫检查点、免疫基质评分等的相关性。结果:P2RX1在LUAD中表达下调,低表达P2RX1的患者预后较差(P<0.05),且P2RX1与肿瘤纯度、分期等临床病理因素有关(P<0.05)。P2RX1的表达与肺鳞癌患者预后无明显相关。Cg06475633等P2RX1 CpG位点甲基化与患者预后相关。P2RX1共表达基因主要富集于免疫细胞活化、分化等通路和生物学进程,核心基因主要包括BTK、IKZF1等。P2RX1的表达与B细胞浸润、免疫/基质评分、PD-1、CTLA-4等多个免疫检查点显著相关(P<0.05)。结论:P2RX1有望成为LUAD诊断和免疫治疗的新靶点。 相似文献
9.
Sung‐Hyun Hwang Myung‐Chul Kim Sumin Ji Yeseul Yang Yeji Jeong Yongbaek Kim 《Cancer science》2019,110(4):1256-1267
Metformin, a drug for type 2 diabetes mellitus, has shown therapeutic effects for various cancers. However, it had no beneficial effects on the survival rate of human malignant mesothelioma (HMM) patients. The present study was performed to elucidate the underlying mechanism of metformin resistance in HMM cells. Glucose‐starved HMM cells had enhanced resistance to metformin, demonstrated by decreased apoptosis and autophagy and increased cell survival. These cells showed abnormalities in mitochondria, such as decreased ATP synthesis, morphological elongation, altered mitochondrial permeability transition pore and hyperpolarization of mitochondrial membrane potential (MMP). Intriguingly, Mdr1 was significantly upregulated in mitochondria but not in cell membrane. The upregulated mitochondrial Mdr1 was reversed by treatment with carbonyl cyanide m‐chlorophenyl hydrazone, an MMP depolarization inducer. Furthermore, apoptosis and autophagy were increased in multidrug resistance protein 1 knockout HMM cells cultured under glucose starvation with metformin treatment. The data suggest that mitochondrial Mdr1 plays a critical role in the chemoresistance to metformin in HMM cells, which could be a potential target for improving its therapeutic efficacy. 相似文献