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41.
Janez Jazbec Lidija Kitanovski Richard Aplenc Maru a Debeljak Vita Dol an 《Leukemia & lymphoma》2005,46(6):893-897
Methylenetetrahydrofolate reductase (MTHFR) polymorphisms have been associated not only with the risk for acute lymphoblastic leukemia (ALL) in adults and children, but also with increased methotrexate toxicity. The present study aimed to investigate whether MTHFR polymorphisms modify the risk for development of secondary malignancies in children treated for ALL with protocols that included high-dose methotrexate. MTHFR genotypes were determined in DNA samples isolated from archived bone marrow smears of 15 patients with a second malignancy and a matched control group of 30 patients who did not developed a second malignancy after the treatment for ALL. The frequencies of MTHFR C677T and A1298C genotypes in all patients were: C677T: CC 40%, CT 46.7% and TT 13.3% and A1298C: AA 46.7%, AC 44.4% and CC 8.9%. The relative risk for second malignancy was not significantly increased in ALL patients having at least one polymorphic C667T [odds ratio (OR) 1.51; 95% confidence interval (CI) 0.43 - 5.31] or one polymorphic A1298C allele (OR 1; 95% CI 0.29 - 3.46). Our study suggests that MTHFR polymorphisms are not associated with increased risk of second cancer in children treated with high-dose methotrexate. 相似文献
42.
目的克隆三七总皂苷甲羟戊酸合成途径中的1个关键酶3-羟基-3-甲基戊二酸单酰辅酶A还原酶(3-hydroxy-3-methylglutaryl coenzyme-A reductase,HMGR)基因,为进一步研究HMGR蛋白的功能及开展三七皂苷的合成生物学研究奠定基础。方法根据NCBI上已公布的同属人参的HMGR基因全长序列(登录号GU565097.1)设计特异性引物。利用RT-PCR技术,以三七愈伤组织总RNA反转录的cDNA为模板扩增基因片段;并对其编码的蛋白进行生物信息学预测和基因表达分析。结果序列分析表明,获得的三七HMGR(命名为PnHMGR)基因的cDNA序列大小为1 893 bp,该序列与人参、刺五加和杜仲中HMGR基因的一致性分别达到98%、93%、80%,且含有大小为1 725 bp的开放阅读框,经Genbank查询为一新的cDNA。生物信息学预测PnHMGR基因编码蛋白包含2个跨膜区,不含信号肽,具有HMGR催化作用的活性中心结构域。实时荧光定量PCR检测到PnHMGR基因在三七细胞生长30 d表达量最高。结论首次从药用植物三七中克隆得到HMGR基因的编码区序列,为进一步鉴定PnHMGR的功能和开展三七皂苷的合成生物学研究奠定了基础。 相似文献
43.
中草药来源的醛糖还原酶抑制剂的研究进展 总被引:15,自引:0,他引:15
中草药作为天然产物,无明显不良反应且来源广泛,以中草药为来源的醛糖还原酶抑制剂其不良反应远低于化学合成及微生物来源的醛糖还原酶抑制剂,在有效阻止和延缓糖尿病并发症如:糖尿病肾病、血管病变、视网膜病变、外周神经病变方面显示了良好的应用前景。作者主要综述了中草药活性成分黄酮类化合物及其衍生物,如:槲皮素、水飞蓟素、葛根素、黄芩苷、黄连素等和一些中药复方制剂,如:参丹健胰丸、筋脉通、六味地黄丸等在抑制醛糖还原酶的活性、降低山梨醇含量等方面取得的研究进展,并对其在治疗糖尿病并发症方面的现状进行了阐述。 相似文献
44.
Human cytochrome P450 2C9 (CYP2C9) accounts for ∼20% of hepatic total CYP content and metabolizes ∼15% clinical drugs such as phenytoin, S-warfarin, tolbutamide, losartan, and many nonsteroidal anti-inflammatory agents (NSAIDs). CYP2C9 is highly polymorphic, with at least 33 variants of CYP2C9 (*1B through *34) being identified so far. CYP2C9*2 is frequent among Caucasians with ∼1% of the population being homozygous carriers and 22% are heterozygous. The corresponding figures for the CYP2C9*3 allele are 0.4% and 15%, respectively. There are a number of clinical studies addressing the impact of CYP2C9 polymorphisms on the clearance and/or therapeutic response of therapeutic drugs. These studies have highlighted the importance of the CYP2C9*2 and *3 alleles as a determining factor for drug clearance and drug response. The CYP2C9 polymorphisms are relevant for the efficacy and adverse effects of numerous NSAIDs, sulfonylurea antidiabetic drugs and, most critically, oral anticoagulants belonging to the class of vitamin K epoxide reductase inhibitors. Warfarin has served as a practical example of how pharmacogenetics can be utilized to achieve maximum efficacy and minimum toxicity. For many of these drugs, a clear gene–dose and gene–effect relationship has been observed in patients. In this regard, CYP2C9 alleles can be considered as a useful biomarker in monitoring drug response and adverse effects. Genetic testing of CYP2C9 is expected to play a role in predicting drug clearance and conducting individualized pharmacotherapy. However, prospective clinical studies with large samples are warranted to establish gene–dose and gene–effect relationships for CYP2C9 and its substrate drugs. 相似文献
45.
按Modest方法合成了11个新的1-(取代萘基-2)-1,2-二氢-2,2-二甲基-4,6-二氨基-1,3,5-三嗪(Ⅴ)。用于合成三嗪的取代-2-萘胺(Ⅵ),也一并在本文中报道。以人早幼粒白血病细胞HL—60测定了(Ⅴ)的抗癌活性。定量构效关系研究表明,(Ⅴ)的抗癌活性与6-取代基的立体参数(MR)呈负相关关系。推测可能是刚性的萘环6-位取代基不为二氢叶酸还原酶的活性空间所容纳的缘故。 相似文献
46.
Guangshuo Li Shang Wang Yunyun Xiong Hongqiu Gu Kaixuan Yang Xin Yang Chunjuan Wang Chuanying Wang Zixiao Li Xingquan Zhao 《CNS Neuroscience & Therapeutics》2022,28(8):1240
IntroductionThe relationship between statins and intracerebral hemorrhage outcomes is unclear.AimWe aimed to compare the in‐hospital mortality and evacuation of intracranial hematoma rates in patients with primary intracerebral hemorrhage between prior statin users and nonusers.ResultsThe final study population included 66,263 patients. Multivariable logistics analyses showed that prior statin use was not associated with in‐hospital mortality for primary intracerebral hemorrhage (adjusted odd ratio 0.78, 95% CI 0.61–1.01), but reduced the proportion of patients undergoing evacuation of intracranial hematoma (adjusted odd ratio 0.70, 95% CI 0.61–0.82). Propensity score matching analyses yielded similar results.ConclusionPrior statin use was not associated with in‐hospital mortality but did reduce evacuation of intracranial hematoma rates. 相似文献
47.
Fenella J. Kirkham Dimitrios Zafeiriou David Howe Philippa Czarpran Ashley Harris Roxanna Gunny Brigitte Vollmer 《European journal of paediatric neurology》2018,22(6):989-1005
Fetal stroke is an important cause of cerebral palsy but is difficult to diagnose unless imaging is undertaken in pregnancies at risk because of known maternal or fetal disorders. Fetal ultrasound or magnetic resonance imaging may show haemorrhage or ischaemic lesions including multicystic encephalomalacia and focal porencephaly. Serial imaging has shown the development of malformations including schizencephaly and polymicrogyra after ischaemic and haemorrhagic stroke. Recognised causes of haemorrhagic fetal stroke include alloimmune and autoimmune thrombocytopaenia, maternal and fetal clotting disorders and trauma but these are relatively rare. It is likely that a significant proportion of periventricular and intraventricular haemorrhages are of venous origin. Recent evidence highlights the importance of arterial endothelial dysfunction, rather than thrombocytopaenia, in the intraparenchymal haemorrhage of alloimmune thrombocytopaenia. In the context of placental anastomoses, monochorionic diamniotic twins are at risk of twin twin transfusion syndrome (TTTS), or partial forms including Twin Oligohydramnios Polyhydramnios Sequence (TOPS), differences in estimated weight (selective Intrauterine growth Retardation; sIUGR), or in fetal haemoglobin (Twin Anaemia Polycythaemia Sequence; TAPS). There is a very wide range of ischaemic and haemorrhagic injury in a focal as well as a global distribution. Acute twin twin transfusion may account for intraventricular haemorrhage in recipients and periventricular leukomalacia in donors but there are additional risk factors for focal embolism and cerebrovascular disease. The recipient has circulatory overload, with effects on systemic and pulmonary circulations which probably lead to systemic and pulmonary hypertension and even right ventricular outflow tract obstruction as well as the polycythaemia which is a risk factor for thrombosis and vasculopathy. The donor is hypovolaemic and has a reticulocytosis in response to the anaemia while maternal hypertension and diabetes may influence stroke risk. Understanding of the mechanisms, including the role of vasculopathy, in well studied conditions such as alloimmune thrombocytopaenia and monochorionic diamniotic twinning may lead to reduction of the burden of antenatally sustained cerebral palsy. 相似文献
48.
Philipp Saiko Geraldine Graser Benedikt Giessrigl Andreas Lackner Michael Grusch Georg Krupitza Arijit Basu Barij Nayan Sinha Venkatesan Jayaprakash Walter Jaeger Monika Fritzer-Szekeres Thomas Szekeres 《Biochemical pharmacology》2011,(1):50
Ribonucleotide reductase (RR; EC 1.17.4.1) is responsible for the de novo conversion of ribonucleoside diphosphates into deoxyribonucleoside diphosphates, which are essential for DNA replication. RR is upregulated in tumor cells and therefore considered to be an excellent target for cancer chemotherapy.ABNM-13 (N-hydroxy-2-(anthracene-2-yl-methylene)-hydrazinecarboximidamide), a novel N-hydroxy-N′-aminoguanidine has been designed to inhibit RR activity using 3D molecular space modeling techniques. In this study, we evaluated its effect on human HL-60 promyelocytic leukemia cells. ABNM-13 proved to be a potent inhibitor of RR which was displayed by significant alterations of deoxyribonucleoside triphosphate (dNTP) pool balance and a highly significant decrease of incorporation of radiolabeled cytidine into DNA of HL-60 cells. Diminished RR activity caused replication stress which was consistent with activation of Chk1 and Chk2, resulting in downregulation/degradation of Cdc25A. In contrast, Cdc25B was upregulated, leading to dephosphorylation and activation of Cdk1. The combined disregulation of Cdc25A and Cdc25B was the most likely cause for ABNM-13 induced S-phase arrest. Finally, we combined ABNM-13 with the first-line antileukemic agent arabinofuranosylcytosine (Ara-C) and found that ABNM-13 synergistically potentiated the antineoplastic effects of Ara-C.Due to these promising results, ABNM-13 deserves further preclinical and in vivo testing. 相似文献
49.
3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂的构效关系研究进展 总被引:1,自引:0,他引:1
3-羟基-3-甲基戊二酰辅酶A(HMG CoA)还原酶抑制剂是治疗高胆固醇血症的有效药物。现综述该类药物的发展概况和作用机制,并从母环、连接链和侧链三部分总结其构效关系,为国内研发新的HMG CoA还原酶抑制剂提供参考。 相似文献
50.
Wangen Wang Yanran HePei Lin Yunfei LiRuifen Sun Wen GuJie Yu Ronghua Zhao 《Journal of ethnopharmacology》2014