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1.
L. Laurian Z. Oberman E. Hoerer E. Graf 《Journal of neural transmission (Vienna, Austria : 1996)》1988,73(3):167-176
Summary In a previous study we observed that calcitonin increases -endorphin, ACTH, and cortisol secretion. We assumed that calcitonin might have a modulatory role on the pituitary function. The present study was initiated to clarify whether this effect is due to a direct pituitary stimulation or to an indirect stimulation through CRF (corticotropin releasing factor).Fourteen healthy subjects, aged 30–60 years were investigated. All the subjects received 100IU Salmon calcitonin Sandoz i.v. at 8a.m. (time 0). Plasma -endorphin, ACTH and cortisol were estimated every 30min from – 30 to 120 min by specific radioimmunoassay. The same parameters were estimated a second time, at the same intervals, when cyproheptadine 8 mg (7 subjects) and 40 mg propranolol (7 subjects) were given per os at – 30 min and calcitonin i.v. at time 0. -endorphin, ACTH and cortisol levels (Mean ±SEM) rose significantly after calcitonin (peak value at 30–90 min) from 5.2 ±0.7 to 15.1±2.6 pmol/l; from 43.0±2.7 to 70.7±4.1 pg/ml and from 10.6±1.5 to 19.6 ±2.1 g/100 ml respectively (p< 0.0001 by analysis of variance and covariance and repeated measures). Propranolol 40 mg (per os) administered at time – 30 did not alter the response of -endorphin, ACTH and cortisol to calcitonin (infused at time 0).Cyproheptadine, the antiserotonergic substance that inhibits the synthesis and release of CRF completely inhibited the stimulatory effect of calcitonin.We conclude that probably calcitonin has a modulatory role on the hypothalamo-pituitary adrenal axis and that it acts at the hypothalamic level probably by stimulating CRF secretion. 相似文献
2.
Bardaro T Falco G Sparago A Mercadante V Gean Molins E Tarantino E Ursini MV D'Urso M 《Human mutation》2003,21(1):8-11
Familial incontinentia pigmenti (IP) is a rare X-linked dominant disorder that affects ectodermal tissues. Over 90% of IP carrier females have a recurrent genomic deletion of exons 4-10 of the NEMO (IKBKG-IKKgamma) gene, which encodes a regulatory component of the IkB kinase complex, required to activate the NF-kB pathway. In IP, mutations in NEMOlead to the complete loss of NF-kB activation creating a susceptibility to cellular apoptosis in response to TNF-alpha. This condition is lethal for males during embryogenesis while females, who are mosaic as a result of X-inactivation, can survive. Recently, a second nonfunctional copy of the gene, DeltaNEMO, was identified, opposite in direction to NEMO in a 35.5-kb duplicated sequence tract. PCR-based detection of the NEMO deletion is diagnostic for IP disease. However, we present instances in which ex 4-10 DeltaNEMO pseudogene deletion occurs in unaffected parents of two females with clinically characteristic IP. These were missed by the currently standard PCR-based method, but can be easily discriminated by a new PCR-based test reported here that permits unambiguous molecular diagnosis and proper familial genetic counseling for IP. 相似文献
3.
目的:研究选择性雌激素受体调节剂(SERM)雷洛昔芬(raloxifene)对血管内皮细胞雌激素应答元件(ERE)转录活性的影响。方法:首先构建ERE荧光素酶报告基因质粒(ERE-TK-Luc),然后采用真核细胞转染技术将ERE-TK-Luc与内参照质粒PRL-SV40一起转染体外培养的血管内皮细胞,检测raloxifene刺激的转染细胞荧光素酶的相对活性,与未用药的转染细胞进行比较。并同时采用raloxifene与雌二醇(E2)共同处理细胞,观察raloxifene对E2作用的影响。结果:在raloxifene处理的转染细胞中荧光素酶表达量低于未用药的转染细胞,raloxifene浓度为10-7mol/L时更明显(P<0.01);E2可使转染细胞荧光素酶表达量明显高于未给药组(P<0.01),而raloxifene与E2同时处理则细胞荧光素酶表达水平与对照组相近(P<0.01)。结论:Raloxifene对血管内皮细胞ERE转录活性有抑制作用。 相似文献
4.
选择性雌激素受体调节剂类乳腺癌治疗新药的研究进展 总被引:3,自引:1,他引:3
选择性雌激素受体调节剂(SERMs)是一系列结构各异的化合物,能与雌激素受体结合,依据靶组织和激素的内环境不同,表现出雌激素激动剂和(或)雌激素拮抗剂的作用,可用于治疗绝经妇女与雌激素水平有关的一系列疾病。综述治疗乳腺癌的SERMs类新药的构效关系研究与开发。 相似文献
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6.
《Drug discovery today》2021,26(12):2816-2838
Glutamatergic transmission is widely implicated in neuropsychiatric disorders, and the discovery that ketamine elicits rapid-acting antidepressant effects by modulating α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) signaling has spurred a resurgence of interest in the field. This review explores agents in various stages of development for neuropsychiatric disorders that positively modulate AMPARs, both directly and indirectly. Despite promising preclinical research, few direct and indirect AMPAR positive modulators have progressed past early clinical development. Challenges such as low potency have created barriers to effective implementation. Nevertheless, the functional complexity of AMPARs sets them apart from other drug targets and allows for specificity in drug discovery. Additional effective treatments for neuropsychiatric disorders that work through positive AMPAR modulation may eventually be developed. 相似文献
7.
《Expert opinion on therapeutic patents》2013,23(11):1297-1306
Critical reassessment of established inotropic drugs such as the phosphodiesterase inhibitors and the digitalis glycosides has reaffirmed the need for novel cardiotonic agents that will not only beneficially affect the haemodynamic and functional impairment of patients with overt congestive heart failure, but also prevent its clinical manifestation and reduce the high mortality. None of the drugs examined in these directions - calcium sensitisers, β-receptor blockers, sodium channel modulators, digitalis derivatives - have been shown to achieve these goals. The research on endogenous digitalis did not, as was hoped, reveal a general strategy for improving the therapeutic index of cardiac glycosides. The proof that Na+/K+-transporting ATPase of cardiac muscle is the molecular point of attack (receptor) for the inotropic and toxic effects of digitalis-like acting C/D-cis and C/D-trans steroids revealed the cyclopentano-perhydrophenanthrene nucleus as their common pharmacophoric lead structure. This has opened a wide field for lead development in the direction of derivatives that favourably discriminate between the inotropy-linked α1-isoform and the toxicity-linked α3-isoform of Na+/K+-ATPase as the basis for the design of inotropic agents with high therapeutic margin. 相似文献
8.
《Expert opinion on investigational drugs》2013,22(4):555-561
Importance of the field: Migraine is an episodic, substantially inherited brain disorder affecting 15% of adults in Western Europe and North America, and is one of the commonest reasons for patients to see their physicians. While the World Health Organization considers that severe migraine can be as disabling as quadriplegia, unfortunately the condition remains undertreated. Until the 1990s, specific migraine therapies were limited to ergot derivatives.Areas covered in this review: The triptans, serotonin 5-HT1B/1D receptor agonists, revolutionized the acute management of migraine patients. However, although the triptans are generally effective and safe, not all patients can take them and many do not respond especially to oral therapies. Recently, progress has been made on the therapeutic front, particularly with new acute treatments. This review will focus on the therapeutic potential of ADX10059, a metabotropic glutamate receptor 5, negative allosteric modulator (mGluR5 NAM), in migraine. Data from a proof-of-concept study in episodic migraineurs demonstrated a significant improvement following acute treatment. A large European multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study is currently investigating the efficacy, safety and tolerability of the compound for migraine prevention.What the reader will gain: The reader will have the basic principles of migraine management and the potential for glutamate-targeted approaches.Take home message: Targeting glutamatergic transmission in migraine may provide a novel preventive therapy that is effective and well-tolerated. 相似文献
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10.
《Archivos de bronconeumologia》2014,50(4):146-150
Cystic fibrosis is a single gene, autosomal recessive disorder, in which more than 1900 mutations grouped into 6 classes have been described. It is an example a disease that could be well placed to benefit from personalized medicine. There are currently 2 very different approaches that aim to correct the basic defect: gene therapy, aimed at correcting the genetic alteration, and therapy aimed at correcting the defect in the CFTR protein. The latter is beginning to show promising results, with several molecules under development. Ataluren (PTC124) is a molecule designed to make the ribosomes become less sensitive to the premature stop codons responsible for class i mutations. Lumacaftor (VX-809) is a CFTR corrector directed at class ii mutations, among which Phe508del is the most frequent, with encouraging results. Ivacaftor (VX-770) is a potentiator, the only one marketed to date, which has shown good efficacy for the class iii mutation Gly551Asp in children over the age of 6 and adults. These drugs, or a combination of them, are currently undergoing various clinical trials for other less common genetic mutations. In the last 5 years, CFTR has been designated as a therapeutic target. Ivacaftor is the first drug to treat the basic defect in cystic fibrosis, but only provides a response in a small number of patients. New drugs capable of restoring the CFTR protein damaged by the most common mutations are required. 相似文献