全文获取类型
收费全文 | 446篇 |
免费 | 23篇 |
国内免费 | 10篇 |
专业分类
耳鼻咽喉 | 18篇 |
儿科学 | 10篇 |
妇产科学 | 10篇 |
基础医学 | 52篇 |
口腔科学 | 14篇 |
临床医学 | 26篇 |
内科学 | 147篇 |
皮肤病学 | 5篇 |
神经病学 | 36篇 |
特种医学 | 2篇 |
外科学 | 58篇 |
综合类 | 1篇 |
预防医学 | 15篇 |
眼科学 | 12篇 |
药学 | 40篇 |
中国医学 | 1篇 |
肿瘤学 | 32篇 |
出版年
2023年 | 3篇 |
2022年 | 11篇 |
2021年 | 15篇 |
2020年 | 5篇 |
2019年 | 12篇 |
2018年 | 10篇 |
2017年 | 19篇 |
2016年 | 14篇 |
2015年 | 15篇 |
2014年 | 18篇 |
2013年 | 26篇 |
2012年 | 34篇 |
2011年 | 32篇 |
2010年 | 13篇 |
2009年 | 26篇 |
2008年 | 27篇 |
2007年 | 35篇 |
2006年 | 35篇 |
2005年 | 27篇 |
2004年 | 24篇 |
2003年 | 14篇 |
2002年 | 9篇 |
2001年 | 3篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1998年 | 5篇 |
1997年 | 3篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 3篇 |
1991年 | 2篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1979年 | 4篇 |
1977年 | 2篇 |
1972年 | 3篇 |
1971年 | 2篇 |
1970年 | 3篇 |
1968年 | 4篇 |
1967年 | 2篇 |
1966年 | 3篇 |
1958年 | 1篇 |
排序方式: 共有479条查询结果,搜索用时 15 毫秒
31.
Ca2+ and Na+ play important roles in neurons, such as in synaptic plasticity. Their concentrations in neurons change dynamically in response to synaptic inputs, but their kinetics have not been compared directly. Here, we show the mechanisms and dynamics of Ca2+ and Na+ transients by simultaneous monitoring in Purkinje cell dendrites in mouse cerebellar slices. High frequency parallel fibre stimulation (50 Hz, 3-50-times) depolarized Purkinje cells, and Ca2+ transients were observed at the anatomically expected sites. The magnitude of the Ca2+ transients increased linearly with increasing numbers of parallel fibre inputs. With 50 stimuli, Ca2+ transients lasted for seconds, and the peak [Ca2+] reached approximately 100 microm, which was much higher than that reported previously, although it was still confined to a part of the dendrite. In contrast, Na+ transients were sustained for tens of seconds and diffused away from the stimulated site. Pharmacological interventions revealed that Na+ influx through alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and Ca2+ influx through P-type Ca channels were essential players, that AMPA receptors did not operate as a Ca2+ influx pathway and that Ca2+ release from intracellular stores through inositol trisphosphate receptors or ryanodine receptors did not contribute greatly to the large Ca2+ transients. 相似文献
32.
Hiroyuki Motoyama Masaru Enomoto Takahiro Yasuda Hideki Fujii Sawako Kobayashi Shuji Iwai Hiroyasu Morikawa Tadashi Takeda Akihiro Tamori Hiroki Sakaguchi Norifumi Kawada 《Nihon Shokakibyo Gakkai zasshi》2008,105(8):1234-1239
A 37-year-old woman was admitted to a hospital with jaundice. Within a couple of weeks, her liver function improved with only symptomatic therapy. About 30 to 60 days before admission, she had taken a herbal medicine, bofu-tsu-sho-san. A diagnosis of drug-induced liver injury was made according to the diagnostic scale proposed at the Digestive Disease Week-Japan 2004. A drug-lymphocyte stimulation test for each ingredient of bofu-tsu-sho-san; the results were positive for Cnidii Rhizoma, Angelicae Radix and Menthae Herba. The liver biopsy specimen revealed features of acute hepatitis. Physicians should be aware that bofu-tsu-sho-san can cause liver injury, as this drug is commonly used as an over-the-counter medicine. 相似文献
33.
34.
The K469E polymorphism of the intercellular adhesion molecule-1 gene is associated with plasma fibrinogen level in type 2 diabetes 总被引:7,自引:0,他引:7
Yokoyama H Tahara H Emoto M Fujiwara S Araki T Shinohara K Hatsuda S Maeno T Shoji T Koyama H Shoji T Nishizawa Y 《Metabolism: clinical and experimental》2005,54(3):381-386
Intercellular adhesion molecule-1 (ICAM-1) is involved in inflammation and development of atherosclerotic change of vascular endothelium. The aim of the present study is to investigate whether K469E polymorphism of the ICAM-1 gene is associated with various clinical factors including plasma fibrinogen in patients with type 2 diabetes. ICAM-1 gene polymorphism was examined using polymerase chain reaction and restriction enzyme analysis in 360 type 2 diabetic patients. Plasma fibrinogen levels and other clinical variables were measured as well as circulating soluble ICAM-1 (sICAM-1) levels by enzyme-linked immunosorbent assay. The distribution of ICAM-1 genotypes, EE, EK, and KK, was not significantly different between type 2 diabetes and 152 healthy control subjects. Among 3 groups according to ICAM-1 genotypes in type 2 diabetes, no difference was found in adiposity, glycemic control, lipid profile, insulin sensitivity evaluated by homeostasis model assessment, or sICAM-1. Regarding fibrinogen, the patients with E allele showed significantly lower plasma fibrinogen levels in a dose-dependent manner (P = .033). Spearman rank correlation analyses revealed that ICAM-1 genotype showed significant correlation with plasma fibrinogen level (P < .001). In multiple regression analysis, ICAM-1 genotype was independent contribution factor of plasma fibrinogen level as well as high-density lipoprotein-cholesterol and urinary albumin excretion (R2 = 0.148, P < .001). In conclusion, K469E polymorphism of the ICAM-1 gene had impact on plasma fibrinogen level independently of other clinical factors in 360 type 2 diabetic patients, suggesting that fibrinogen is a candidate which links the ICAM-1 gene polymorphism to atherosclerosis. 相似文献
35.
36.
Miho Shimizu Kengo Furuichi Tadashi Toyama Tomoaki Funamoto Shinji Kitajima Akinori Hara Daisuke Ogawa Daisuke Koya Kenzo Ikeda Yoshitaka Koshino Yukie Kurokawa Hideharu Abe Kiyoshi Mori Masaaki Nakayama Yoshio Konishi Ken-ichi Samejima Masaru Matsui Hiroyuki Yamauchi Tomohito Gohda Kei Fukami Daisuke Nagata Hidenori Yamazaki Yukio Yuzawa Yoshiki Suzuki Shouichi Fujimoto Shoichi Maruyama Sawako Kato Takero Naito Kenichi Yoshimura Hitoshi Yokoyama Takashi Wada Research Group of Diabetic Nephropathy the Ministry of Health Labour Welfare of Japan Japan Agency for Medical Research Development 《Clinical and experimental nephrology》2018,22(2):377-387
Background
There is increased interest in surrogate endpoints for clinical trials of chronic kidney disease.Methods
In this nationwide observational study of 456 patients with type 2 diabetes and clinically suspected diabetic nephropathy followed for a median of 4.2 years, we evaluated the association between estimated glomerular filtration rate (eGFR) and albuminuria at baseline or during follow-up and risk of ESRD.Results
Low eGFR (<60 mL/min/1.73 m2) and macroalbuminuria at enrollment were independently associated with risk of ESRD. In patients with macroalbuminuria, both ≤?50% change and ?50 to ?30% change in eGFR over 1 and 2 years were predictive of ESRD. The higher cut point (≥50% decline in eGFR) was more strongly predictive but less common. Remission of macroalbuminuria to normo-/microalbuminuria at 1 and 2 years was associated with a lower incidence of ESRD than no remission; however, it was not a determinant for ESRD independently of initial eGFR and initial protein-to-creatinine ratio.Conclusion
These results suggest that a ≥30% decline in eGFR over 1 or 2 years adds prognostic information about risk for ESRD in patients with type 2 diabetes and macroalbuminuria, supporting the consideration of percentage decline in eGFR as a surrogate endpoint among macroalbuminuric cases in type 2 diabetes. On the other hand, our study suggests that additional analyses on the relationship between remission of macroalbuminuria and risk of ESRD are needed in type 2 diabetes.37.
Atarashi H Kuruma A Yashima M Saitoh H Ino T Endoh Y Hayakawa H 《Clinical pharmacology and therapeutics》2000,68(2):143-150
OBJECTIVES: To elucidate pharmacokinetics and pharmacodynamics of landiolol hydrochloride, newer developed ultra-short-acting beta-blocker, in patients with various cardiac tachyarrhythmias. BACKGROUND: The short duration of action and titratability of landiolol hydrochloride make it ideal for use in patients with a clinical need for beta-blockers. METHODS: In a total of 31 examinations we infused the drug in 19 patients (mean age, 55 +/- 14 years). After the persistence of the tachyarrhythmias was confirmed, continuous infusion was started at rates of 0.005, 0.01, 0.02, 0.04, and 0.08 mg/kg/min for 5 minutes (for paroxysmal atrial fibrillation, paroxysmal supraventricular tachycardia, and ventricular tachycardia) or 15 minutes (for ventricular premature complex). We analyzed the pharmacokinetics of 16 examinations. A one-compartment model provided a close fit for each blood concentration-time curve. RESULTS: The maximum blood concentrations obtained clearly showed the dose dependency and revealed very short half-lives (range, 2.3 to 4.0 minutes). Area under the blood concentration-time curves also increased, showing dose dependency. In paroxysmal atrial fibrillation, landiolol hydrochloride reduced the heart rate from 111 +/- 20 to 90 +/- 10/min. Sinus rhythm was restored, without any adverse effects, in three of five patients with paroxysmal supraventricular tachycardia and one patient with ventricular tachycardia. There was no significant change in peripheral blood pressure. CONCLUSIONS: Landiolol hydrochloride has a shorter elimination half-life than any other beta-blocker, and it can be administered safely to patients with various tachyarrhythmias. 相似文献
38.
Naya M Kobayashi N Ema M Kasamoto S Fukumuro M Takami S Nakajima M Hayashi M Nakanishi J 《Regulatory toxicology and pharmacology : RTP》2012,62(1):1-6
Titanium dioxide (TiO2) is widely used as a white pigment in paints, plastics, inks, paper, creams, cosmetics, drugs and foods. In the present study, the genotoxicity of anatase TiO2 nanoparticles was evaluated in vivo using the comet assay after a single or repeated intratracheal instillation in rats. The nanoparticles were instilled intratracheally at a dosage of 1.0 or 5.0 mg/kg body weight (single instillation group) and 0.2 or 1.0 mg/kg body weight once a week for 5 weeks (repeated instillation group) into male Sprague–Dawley rats. A positive control, ethyl methanesulfonate (EMS) at 500 mg/kg, was administered orally 3 h prior to dissection. Histopathologically, macrophages and neutrophils were detected in the alveolus of the lung in the 1.0 and 5.0 mg/kg TiO2 groups. In the comet assay, there was no increase in % tail DNA in any of the TiO2 groups. In the EMS group, there was a significant increase in % tail DNA compared with the negative control group. TiO2 nanoparticles in the anatase crystal phase are not genotoxic following intratracheal instillation in rats. 相似文献
39.
Sawako Arai Kazuhiro Takuma Hiroyuki Mizoguchi Daisuke Ibi Hiroyuki Kamei Kiyofumi Yamada 《European journal of pharmacology》2009,602(1):101-641
In this study, we investigated the effects of GABAA and GABAB receptor agonists on the methamphetamine-induced impairment of recognition memory in mice. Repeated treatment with methamphetamine at a dose of 1 mg/kg for 7 days induced an impairment of recognition memory. Baclofen, a GABAB receptor agonist, ameliorated the repeated methamphetamine-induced cognitive impairment, although gaboxadol, a GABAA receptor agonist, had no significant effect. GABAB receptors may constitute a putative new target in treating cognitive deficits in patients suffering from schizophrenia, as well as methamphetamine psychosis. 相似文献
40.
Overexpression of gamma-glutamyltransferase in transgenic mice accelerates bone resorption and causes osteoporosis 总被引:1,自引:0,他引:1
Hiramatsu K Asaba Y Takeshita S Nimura Y Tatsumi S Katagiri N Niida S Nakajima T Tanaka S Ito M Karsenty G Ikeda K 《Endocrinology》2007,148(6):2708-2715
We previously identified gamma-glutamyltransferase (GGT) by expression cloning as a factor inducing osteoclast formation in vitro. To examine its pathogenic role in vivo, we generated transgenic mice that overexpressed GGT in a tissue-specific manner utilizing the Cre-loxP recombination system. Systemic as well as local production of GGT accelerated osteoclast development and bone resorption in vivo by increasing the sensitivity of bone marrow macrophages to receptor activator of nuclear factor-kappaB ligand, an essential cytokine for osteoclastogenesis. Mutated GGT devoid of enzyme activity was as potent as the wild-type molecule in inducing osteoclast formation, suggesting that GGT acts not as an enzyme but as a cytokine. Recombinant GGT protein increased receptor activator of nuclear factor-kappaB ligand expression in marrow stromal cells and also stimulated osteoclastogenesis from bone marrow macrophages at lower concentrations. Thus, GGT is implicated as being involved in diseases characterized by accelerated osteoclast development and bone destruction and provides a new target for therapeutic intervention. 相似文献