全文获取类型
收费全文 | 2042篇 |
免费 | 130篇 |
国内免费 | 95篇 |
专业分类
耳鼻咽喉 | 27篇 |
儿科学 | 32篇 |
妇产科学 | 16篇 |
基础医学 | 289篇 |
口腔科学 | 24篇 |
临床医学 | 110篇 |
内科学 | 385篇 |
皮肤病学 | 11篇 |
神经病学 | 271篇 |
特种医学 | 26篇 |
外科学 | 111篇 |
综合类 | 192篇 |
预防医学 | 66篇 |
眼科学 | 18篇 |
药学 | 512篇 |
中国医学 | 41篇 |
肿瘤学 | 136篇 |
出版年
2023年 | 16篇 |
2022年 | 44篇 |
2021年 | 53篇 |
2020年 | 48篇 |
2019年 | 36篇 |
2018年 | 35篇 |
2017年 | 43篇 |
2016年 | 42篇 |
2015年 | 63篇 |
2014年 | 85篇 |
2013年 | 154篇 |
2012年 | 95篇 |
2011年 | 157篇 |
2010年 | 110篇 |
2009年 | 126篇 |
2008年 | 155篇 |
2007年 | 111篇 |
2006年 | 110篇 |
2005年 | 89篇 |
2004年 | 80篇 |
2003年 | 76篇 |
2002年 | 57篇 |
2001年 | 42篇 |
2000年 | 41篇 |
1999年 | 35篇 |
1998年 | 33篇 |
1997年 | 34篇 |
1996年 | 36篇 |
1995年 | 18篇 |
1994年 | 28篇 |
1993年 | 25篇 |
1992年 | 17篇 |
1991年 | 15篇 |
1990年 | 13篇 |
1989年 | 11篇 |
1988年 | 12篇 |
1987年 | 14篇 |
1986年 | 7篇 |
1985年 | 13篇 |
1984年 | 7篇 |
1983年 | 7篇 |
1981年 | 6篇 |
1980年 | 6篇 |
1979年 | 8篇 |
1976年 | 5篇 |
1975年 | 4篇 |
1974年 | 7篇 |
1973年 | 10篇 |
1972年 | 8篇 |
1971年 | 5篇 |
排序方式: 共有2267条查询结果,搜索用时 15 毫秒
41.
Peggy Papeleu Tamara Vanhaecke Greetje Elaut Mathieu Vinken Tom Henkens Sarah Snykers 《Critical reviews in toxicology》2013,43(4):363-378
Histone deacetylase (HDAC) inhibitors target key steps of tumor development: They inhibit proliferation, induce differentiation and/or apoptosis, and exhibit potent antimetastatic and antiangiogenic properties in transformed cells in vitro and in vivo. Preliminary studies in animal models have revealed a relatively high tumor selectivity of HDAC inhibitors, strenghtening their promising potential in cancer chemotherapy. Until now, preclinical in vitro research has almost exclusively been performed in cancer cell lines and oncogene-transformed cells. However, as cell proliferation and apoptosis are essential for normal tissue and organ homeostasis, it is important to investigate how HDAC inhibitors influence the regulation of and interplay between proliferation, differentiation, and apoptosis in primary cells as well. This review highlights the discrepancies in molecular events triggered by trichostatin A, the reference compound of hydroxamic acid-containing HDAC inhibitors, in hepatoma cells and primary hepatocytes (which are key targets for drug-induced toxicity). The implications of these differential outcomes in both cell types are discussed with respect to both toxicology and drug development. In view of the future use of HDAC inhibitors as cytostatic drugs, it is highly recommended to include both tumor cells and their healthy counterparts in preclinical developmental studies. Screening the toxicological properties of compounds early in their development process, using a battery of different cell types, will enable researchers to discard those compounds bearing undesirable adverse activity before entering into expensive clinical trials. This will not only reduce the risk for harmful exposure of patients but also save time and money. 相似文献
42.
《European neuropsychopharmacology》2014,24(5):788-799
The past decade has witnessed a resurgence of interest in the development of novel pharmacological agents to treat the negative symptoms of schizophrenia. This review provides an overview of pharmacological approaches that have been evaluated as potential treatments and describes the emergence of several promising new approaches. First, we briefly describe recent methodological developments, including consensus-based clinical trial guidelines for patient selection criteria, symptom assessment, and trial duration. Next, we overview mono- and adjunctive-therapies that have been evaluated, including first- and second-generation antipsychotics, antidepressants, psychostimulants, molecules targeting cholinergic and glutamatergic systems, and hormones. We highlight the most promising pharmacological agents on the horizon, including glycine transporter-1 inhibitors, α7-nicotinic receptor positive allosteric modulators, and oxytocin, as well as non-pharmacological electromagnetic stimulation approaches. Further investigations, using optimal clinical trial design, hold considerable promise for discovering effective treatments for these functionally disabling symptoms in the near future. 相似文献
43.
细菌分泌系统的发现是近年来细菌致病机制研究的重点。致病菌为在宿主体内生存、繁殖、扩散,会分泌一些蛋白性质的毒性因子。目前认为革兰阴性致病菌在长期进化过程中形成入侵宿主细胞的特异性分泌系统共有5种类型(I~V型),其中最显著的是细菌Ⅲ型分泌系统(type three secretion system, T3SS),与细菌致病性密切相关。T3SS抑制剂的策略是细菌分泌毒力蛋白,阻止其对宿主细胞的侵染。本文对细菌T3SS的组成、T3SS抑制剂筛选系统、T3SS抑制剂以及作用机制等进行综述,为深入研究以T3SS为靶点的药物设计提供参考。 相似文献
44.
AbstractGlycine is an amino acid neurotransmitter found in the spinal cord and is closely associated with interneurons that modulate afferent activity. We have previously shown that low segmental glycine concentrations or blockade of normal glycinergic activity lowers the threshold for pain thresholds. In addition, intrathecal glycine infusion increases the pain threshold in animal models of neuropathic pain. However, the role of the glycine receptor in neuropathic pain is not clear and is the basis for the current study. Using a unilateral sciatic nerve constriction injury model of neuropathic pain, the strychnine sensitive glycine receptor population was studied using immunohistochemical techniques. Glycine receptors are reduced in number in the dorsal horn bilaterally in injured animals. Glycine and related compounds are potentially valuable agents for treating chronic pain conditions in humans. A better understanding of glycine-receptor interactions should prove valuable as these compounds are studied in greater depth. [Neural Res 1998; 20: 161–168] 相似文献
45.
M. Blackberg K. Ohlsson 《Scandinavian journal of clinical and laboratory investigation》2013,73(1):57-67
Tissue kallikrein is released in the body both physiologically and in many inflammatory disorders. Little is, however, known about the turnover of released tissue kallikrein in humans. Approximately 1 mg of tissue kallikrein (mol wt 43 000 Da) was purified from 85 L human urine by: (1) ultracentrifugation, (2) filtration through an aprotinin-coupled Sepharose 4B column, followed by (3) gel filtration over a Sephadex G-75 column. The elimination, after intraduodenal or intravenous administration of purified tissue kallikrein radiolabelled with 125I, was followed by collecting serial samples of plasma, urine and faeces from three volunteers. Within 72 h, about 96% of the intraduodenally administered radioactivity had been excreted in urine, and approximately 5.4% in faeces, mainly as 125I. No intact 125I-tissue kallikrein was found in plasma, urine or faeces after the intraduodenal instillation of the protein. The plasma half-life of 125I-tissue kallikrein up to 3 h after intravenous injection was 9 min and, thereafter, 20 h. The 125I-tissue kallikrein was quickly bound to a plasma protein with a mol wt of about 67 kDa, but some of the radioiodinated tissue kallikrein was still unbound 15 min after injection, judged by gel filtration on Sephadex G-200 columns. Most of the radioactivity was excreted in the urine as 125I, but about 4- 6% was recovered as free 125I-tissue kallikrein. Conclusion: The use of tissue kallikrein as an oral drug appears, therefore, to be useless. Tissue kallikrein released into plasma seems to be quickly bound to a protein with a mol wt of 67 kDa, probably kallistatin or Protein C inhibitor, but some tissue kallikrein seems to be unbound and may have some physiological or pathophysiological action. The unbound tissue kallikrein is, at least partly, cleared from the circulation by the kidneys, and tissue kallikrein in the urine may partly be derived from plasma. 相似文献
46.
非经典型蛋白激酶C是G蛋白偶联受体系统中的效应物,其在细胞内信号传递过程中起重要作用,可介导细胞增殖和分化、影响细胞周期和细胞凋亡、参与代谢调节、促进肿瘤形成和转移等。因此,靶向非经典型蛋白激酶C的药物在疾病治疗中有广泛的应用前景。 相似文献
47.
Pentameric ligand-gated ion channels mediate rapid chemo-electric signal transduction in animals. The active site of this family of proteins is their ion channel pore, which is located at the center of the transmembrane domain. The opening/closing motions of the channel pore are governed by the binding of neurotransmitter to the extracellular domain, but also by allosteric effectors acting within the transmembrane domain. Here, we review the structure of the transmembrane domain as well as its role in the allosteric modulation of pentameric ligand-gated ion channel function. We focus on two examples: the interactions of nicotinic ACh receptors with lipids, for which a novel “uncoupled” state has been proposed, and the interactions of GABAA and Glycine receptors with allosteric modulators, such as general anesthetics, ethanol and neurosteroids. We revisit these data in light of the recently solved X-ray structures of bacterial members of the family, which provide atomic-resolution insight into the structures of both the transmembrane domain and associated lipids. 相似文献
48.
49.
摘 要 分泌性腹泻威胁着全球健康,是儿童发病和死亡的主要原因之一。肠上皮细胞腔内Cl-通道激活导致肠道液体过度分泌是肠毒素引起腹泻的主要原因。在霍乱及其他细菌肠毒素引发的腹泻中,囊性纤维化跨膜传导调节因子(cystic fibrosis transmembrane conductance regulator, CFTR)是主要的cAMP-调节Cl 通道,其主要功能是促进上皮细胞液体分泌。利用肠上皮细胞CFTR抑制药抗分泌性腹泻是一种新途径。已有的CFTR抑制药有噻唑啉酮类、甘氨酸酰肼类和喹喔啉二酮等。同时,从天然植物中提取分离的一些成分也具有CFTR抑制作用,但研究还不够深入。因此,对CFTR抑制药的研究进展进行了综述。 相似文献
50.
Abdulkerim Yıldız Osman Şahin Okan Yayar Çiğdem Pala Öztürk Hacer Berna Afacan Öztürk Senem Maral Harika Okutan Murat Albayrak 《Transfusion and apheresis science》2018,57(3):398-400
Hemophilia is a hereditary disease with impaired blood coagulation due to a genetic deficiency of blood coagulation factors. The development of inhibitors further complicates the course of the disease and management. The case is here reported of a haemophilia patient who presented with coexisting development of high titer inhibitor with Gastrointestinal Stromal Tumor (GIST) diagnosis and was admitted with upper gastrointestinal system bleeding. The patient had no prior history of inhibitor presence. During all procedures including surgery, excellent hemostasis was achieved with rFVIIa treatment and no hemorrhagic complication was observed. To the best of our knowledge, this constitutes the first reported case of GIST associated with inhibitor development in a hemophilia A patient. 相似文献