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991.
Ohmori T Yano Y Sakata A Ikemoto T Shimpo M Madoiwa S Katsuki T Mimuro J Shimada K Kario K Sakata Y 《Thrombosis research》2012,129(4):e36-e40
High residual platelet aggregability during thienopyridine treatment occurs because of low levels of the active drug metabolite, and is associated with an increased rate of major adverse cardiovascular events. Recent findings suggest that paraoxonase-1 (PON1) is a major determinant for clopidogrel efficacy. The aim of this study was to assess the impact of serum PON1 activity on platelet aggregability in thienopyridine-treated patients. In 72 patients receiving treatment with aspirin and ticlopidine after acute coronary syndrome, various laboratory data including the formation of platelet aggregations induced by agonists were compared with serum PON1 activities, measured as paraoxonase and homocysteine thiolactone hydrolase (HTLase). Serum paraoxonase activity was significantly associated with HTLase activity (R = 0.4487, P < 0.0001). These PON1 activities were not correlated with any parameters for platelet aggregation, hypertension, sleep apnea, and diabetes mellitus. In contrast, serum PON1 activities seemed to be involved in cardiac function, with brain natriuretic peptide and ejection fraction being significantly correlated with serum HTLase activity (R = − 0.2767, P = 0.0214) and paraoxonase activity (R = 0.2558, P = 0.0339), respectively. Paraoxonase activity also demonstrated a significant association with increased levels of ankle-brachial index (R = 0.267, P = 0.0255). Serum PON1 activities did not influence platelet aggregability during treatment with thienopyridine. However, they might modulate cardiac function after acute coronary syndrome and progression of atherosclerosis. 相似文献
992.
阿伐他汀对亚糖尿病大鼠血糖的影响及其机制 总被引:2,自引:2,他引:0
研究阿伐他汀对亚糖尿病大鼠血糖的影响及其机制。用链脲佐菌素(35mg/kg)诱发亚糖尿病大鼠,并分别用阿伐他汀(20,100 mg/kg)治疗2周后,进行葡萄糖耐量实验,测定相应的胰岛素水平;测定肝微粒体中CYP3A1/2和CYP2C9的活性,并测定肝脏和胰腺中CYP3A1/2 mRNA表达。在细胞水平考察阿伐他汀对HepG2细胞糖利用、CYP3A酶以及ROS生成的影响,并考察阿伐他汀对INS-1细胞胰岛素释放以及ROS生成的影响。结果显示,低剂量阿伐他汀可以损伤亚糖尿病大鼠的糖耐量。CYP3A、CYP2C酶活性出现轻微增加,QT-PCR结果显示肝脏和胰腺中CYP3A1/2 mRNA表达也被低剂量阿伐他汀诱导。离体实验结果表明,阿伐他汀对HepG2细胞CYP3A酶活性呈现了低剂量诱导、高剂量抑制的现象。同时,阿伐他汀还可以剂量依赖性地降低HepG2细胞的糖利用,并增加HepG2细胞ROS水平,这一作用可以被CYP3A抑制剂红霉素逆转;阿伐他汀在抑制INS-1细胞胰岛素释放的同时,也能增加INS-1细胞活性氧(ROS)含量,这种作用也可被红霉素逆转。上述结果显示,阿伐他汀加重亚糖尿病的作用可能与其诱导P450酶和ROS过度生成有关。 相似文献
993.
Background and objective: CYP2C19 is a drug‐metabolizing enzyme showing various genetic polymorphisms that may cause marked interindividual and interethnic variability in the disposition of its substrates. We assessed CYP2C19 genetic polymorphisms in a Korean population using a newly developed multiplex pyrosequencing method. Method: A multiplex pyrosequencing method to simultaneously detect CYP2C19*2, *3, and *17 alleles was designed. We established the frequency of these CYP2C19 alleles in 271 Korean subjects using the multiplex pyrosequencing method. Results: The results showed 100% concordance between single and multiplex pyrosequencing methods. We also validated the polymorphisms identified by pyrosequencing with direct sequencing method. The allele frequencies of CYP2C19*2, CYP2C19*3, and CYP2C19*17 were 0·284, 0·101 and 0·015 respectively. These frequencies are similar to that reported for other Asian populations including Japanese and Chinese but different from that of Caucasians and Africans. Conclusions: The multiplex pyrosequencing method to detect CYP2C19*2, CYP2C19*3, and CYP2C19*17 concurrently, seems to be a rapid and reliable genotyping method for the detection of important CYP2C19 genetic polymorphisms. Similar to studies conducted on other Asian populations, this study reported that in the Korean population tested, the CYP2C19*2 and CYP2C19*3 alleles were relatively frequently found, whereas the frequency of CYP2C19*17 was very low. 相似文献
994.
What is known and objective: Genetic polymorphism of interleukin (IL)–1β and IL‐1 receptor antagonist (IL‐1rα) are associated with efficacy of acid suppression, whereas cytochrome P (CYP) 2C19 polymorphism influences the metabolism of proton pump inhibitor family. Thus, CYP2C19 and IL‐1 polymorphisms may affect the efficacy of H. pylori eradication therapy. We compared the efficacies of omeprazole and rabeprazole on eradication of H. pylori in relation to CYP2C19, IL‐1B and IL‐1RN genotypes in Chinese people. Methods: Two hundred and forty Chinese with peptic ulcer disease were randomly assigned to the following regimens: amoxicillin and clarithromycin together with omeprazole (OAC) or rabeprazole (RAC). CYP2C19*2 and *3, IL1B‐511, IL1B‐31, IL1B+ 3954 and intron 2 of the IL‐1RN genotypes were analyzed by polymerase chain reaction‐restriction fragment length polymorphism. Results: The intention‐to‐treat‐based cure rate of the OAC regimen was significantly lower than that of the RAC regimen in the CYP2C19 wild‐type homozygotes (P = 0·014). No significant differences in the cure rates were observed among the IL‐1RN and the IL‐1B genotype groups. What is new and conclusions: The rabeprazole‐based triple regimen was better than the omeprazole in Chinese patients with the CYP2C19 extensive metabolizer genotype. The effectiveness of the PPI/AC regimen is unrelated to IL‐1B and IL1‐RN genetic polymorphism. 相似文献
995.
996.
Cytochrome P450 metabolites of arachidonic acid: novel regulators of renal function. 总被引:1,自引:0,他引:1
K M Hoagland K G Maier C Moreno M Yu R J Roman 《Nephrology, dialysis, transplantation》2001,16(12):2283-2285
997.
998.
细胞色素P450与肿瘤 总被引:1,自引:0,他引:1
当今社会,恶性肿瘤患者日益增多,而且恶性肿瘤的化疗药物的治疗窗很窄,相同剂量的药物在化疗疗效和毒性反应方面存在很大的个体差异。因此,研究肿瘤的发生及个体化治疗成为当前的热点问题。细胞色素P450酶系是自然界中含量最丰富、分布最广泛、底物谱最广的Ⅰ相代谢酶系。本文就细胞色素P450酶系对肿瘤的发生、治疗关系作一综述。 相似文献
999.
Purpose To assess the potential for drug–drug interactions between lenalidomide and substrates and inhibitors of cytochrome P450 (CYP)
isozymes.
Methods In vitro metabolism of lenalidomide by human liver microsomes, recombinant human CYPs and human hepatocytes was evaluated.
The inhibitory and inductive effects of lenalidomide on the CYP activities were evaluated in human liver microsomes and cultured
human hepatocytes, respectively.
Results In vitro incubation of lenalidomide with human liver microsomes, recombinant-CYP isozymes, and human hepatocytes did not result
in Phase I or Phase II metabolism, confirming the low propensity of lenalidomide for metabolism in vivo in humans. In vitro,
lenalidomide did not inhibit CYP isozymes in human liver microsomes and did not induce CYP activities in cultured human hepatocytes.
Conclusions Lenalidomide is not a substrate, inhibitor, or inducer of CYP group of enzymes; clinically relevant pharmacokinetic drug–drug
interactions are unlikely to occur between lenalidomide and co-administered CYP substrates or inhibitors. 相似文献
1000.
河南汉族人群细胞色素P-450 1A1与肺癌易感性的关系 总被引:1,自引:0,他引:1
目的:探讨CYP1A1基因多态与支气管肺癌癌变关系。方法:采用病例-对照设计和PCR-RFLP方法,检测肺癌组103例和对照组138例CYP1A1基因多态,以logistic回归模型计算比数比(odds ratios,OR)及95%可信区间(confidential intervals,CI)。结果:CYP1A1m1突变型等位基因频率在对照组和肺癌组分别为27.6%和42.7%。logistic回归分析表明,CYP1A1(w1/m1)杂合型(B型)和(m1/m1)纯合突变型(C型)患肺癌的危险度分别升高3.19和2.61倍,差异显著。结论:CYP1A m1突变型等位基因是患肺癌的危险因素。 相似文献