全文获取类型
收费全文 | 405篇 |
免费 | 44篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 15篇 |
基础医学 | 37篇 |
口腔科学 | 3篇 |
临床医学 | 78篇 |
内科学 | 75篇 |
皮肤病学 | 3篇 |
神经病学 | 100篇 |
特种医学 | 10篇 |
外科学 | 16篇 |
综合类 | 6篇 |
预防医学 | 6篇 |
眼科学 | 5篇 |
药学 | 90篇 |
中国医学 | 1篇 |
肿瘤学 | 4篇 |
出版年
2018年 | 3篇 |
2016年 | 3篇 |
2015年 | 6篇 |
2013年 | 2篇 |
2012年 | 5篇 |
2011年 | 6篇 |
2010年 | 3篇 |
2008年 | 6篇 |
2007年 | 7篇 |
2006年 | 4篇 |
2004年 | 8篇 |
2003年 | 12篇 |
2002年 | 5篇 |
2000年 | 9篇 |
1999年 | 7篇 |
1998年 | 13篇 |
1997年 | 13篇 |
1996年 | 19篇 |
1995年 | 7篇 |
1994年 | 4篇 |
1993年 | 6篇 |
1992年 | 8篇 |
1991年 | 9篇 |
1990年 | 10篇 |
1989年 | 14篇 |
1988年 | 11篇 |
1987年 | 13篇 |
1986年 | 8篇 |
1985年 | 14篇 |
1984年 | 11篇 |
1983年 | 12篇 |
1982年 | 10篇 |
1981年 | 18篇 |
1980年 | 6篇 |
1979年 | 20篇 |
1978年 | 11篇 |
1977年 | 6篇 |
1976年 | 10篇 |
1975年 | 12篇 |
1974年 | 10篇 |
1973年 | 11篇 |
1972年 | 11篇 |
1971年 | 15篇 |
1970年 | 10篇 |
1969年 | 6篇 |
1968年 | 7篇 |
1967年 | 4篇 |
1966年 | 6篇 |
1965年 | 3篇 |
1964年 | 2篇 |
排序方式: 共有450条查询结果,搜索用时 15 毫秒
91.
92.
H Tamary C Kaplinsky I Levy IJ Cohen I Yaniv B Stark Y Goshen R Zaizov 《Acta paediatrica (Oslo, Norway : 1992)》1994,83(9):931-934
An understanding of the natural history of childhood chronic idiopathic thrombocytopenia purpura (ITP) could contribute to a rational therapeutic approach to its treatment, which remains controversial. In our retrospective study of 92 children with ITP, 22 had a chronic course and were followed for 3–14 years (median 8.6 years). Treatment, when indicated, was individualized: 4 patients (18.2%) did not receive any treatment, 14 (63.6%) received steroids only, while 4 (18.2%) were treated with steroids and one of the following: high-dose gamma globulin (4 patients), splenectomy (2 patients) or immunosuppressive therapy (2 patients). During follow-up, 14 patients (63.6%) achieved complete remission, 5 (22.7%) partial remission and only 3 (13.5%) remained severely thrombocytopenic, with minimal bleeding tendency. Eleven patients (50%) responded to the initial prednisone course (1–5mg/kg/day), but showed a marked decrease in platelet count when steroids were tapered off. In view of the high rates of complete and partial remission and the mild course of the few non-responding patients, it is suggested that with adequate supportive therapy, follow-up problems and fatalities can be kept to a minimum. We believe that aggressive therapy, such as splenectomy, should be reserved for the rare symptomatic and severely thrombocytopenic patient. 相似文献
93.
Lamensdorf I He L Nechushtan A Harvey-White J Eisenhofer G Milan R Rojas E Kopin IJ 《European journal of pharmacology》2000,388(2):147-154
Sulfonylureas block ATP-dependent K(+) channels (K/ATP channels) in pancreatic beta cells and brain gamma-aminobutyric acid (GABA) containing neurons causing depolarization-evoked insulin or GABA release. In high concentrations, sulfonylureas also inhibit catecholamine release from bovine adrenal chromaffin cells and isolated guinea pig aorta. In this study, we examined the effect of glipizide, a sulfonylurea, on dopamine release from PC12 cells and found that neither basal nor K(+)-stimulated dopamine release was affected. Although PC12 cells expressed mRNA for the K/ATP channel, functional K/ATP channels could not be demonstrated electrophysiologically, consistent with the lack of effect of glipizide on dopamine release. Glipizide did, however, increase cytoplasmic retention of the acidic dopamine metabolites, 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), indicating blockade of their outward transport. The cellular accumulation of DOPAC was accompanied by reduced tyrosine hydroxylase activity and reduced formation of dopamine and its metabolites presumably by a negative feedback effect of the increased cytoplasmic concentrations of DOPAC. 相似文献
94.
Lamensdorf I Hrycyna C He LP Nechushtan A Tjurmina O Harvey-White J Eisenhofer G Rojas E Kopin IJ 《Naunyn-Schmiedeberg's archives of pharmacology》2000,361(6):654-664
Incubation of PC 12 cells with the sulfonylurea drug, glipizide (1-100 microM), increased intracellular levels of the acidic metabolites of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). The levels of these acids in the medium were decreased, indicating the presence of a sulfonylurea-sensitive organic anion transporter. In the present study, we demonstrate that the sulfonylurea-sensitive transport of acidic dopamine metabolites is unidirectional, ATP dependent, unaffected by ouabain or by tetrodotoxin and blocked by drugs that interact with the multidrug-resistance protein-1 (MRP1). However, over-expression of MRP1 did not affect transport of the acid metabolites. The pharmacological profile and ion dependence of the transporter also differs from that of known ATP-binding cassette (ABC) family members. Using microdialysis, we also demonstrated a sulfonylurea-sensitive transport process in the striatum of freely moving rats. These results show that acidic dopamine metabolites are actively secreted from dopaminergic cells into surrounding extracellular fluid by a previously undescribed transporter. 相似文献
95.
Catecholamine metabolism: a contemporary view with implications for physiology and medicine 总被引:1,自引:0,他引:1
This article provides an update about catecholamine metabolism, with emphasis on correcting common misconceptions relevant to catecholamine systems in health and disease. Importantly, most metabolism of catecholamines takes place within the same cells where the amines are synthesized. This mainly occurs secondary to leakage of catecholamines from vesicular stores into the cytoplasm. These stores exist in a highly dynamic equilibrium, with passive outward leakage counterbalanced by inward active transport controlled by vesicular monoamine transporters. In catecholaminergic neurons, the presence of monoamine oxidase leads to formation of reactive catecholaldehydes. Production of these toxic aldehydes depends on the dynamics of vesicular-axoplasmic monoamine exchange and enzyme-catalyzed conversion to nontoxic acids or alcohols. In sympathetic nerves, the aldehyde produced from norepinephrine is converted to 3,4-dihydroxyphenylglycol, not 3,4-dihydroxymandelic acid. Subsequent extraneuronal O-methylation consequently leads to production of 3-methoxy-4-hydroxyphenylglycol, not vanillylmandelic acid. Vanillylmandelic acid is instead formed in the liver by oxidation of 3-methoxy-4-hydroxyphenylglycol catalyzed by alcohol and aldehyde dehydrogenases. Compared to intraneuronal deamination, extraneuronal O-methylation of norepinephrine and epinephrine to metanephrines represent minor pathways of metabolism. The single largest source of metanephrines is the adrenal medulla. Similarly, pheochromocytoma tumor cells produce large amounts of metanephrines from catecholamines leaking from stores. Thus, these metabolites are particularly useful for detecting pheochromocytomas. The large contribution of intraneuronal deamination to catecholamine turnover, and dependence of this on the vesicular-axoplasmic monoamine exchange process, helps explain how synthesis, release, metabolism, turnover, and stores of catecholamines are regulated in a coordinated fashion during stress and in disease states. 相似文献
96.
Bridging the treatment gap: improving compliance with lipid-modifying agents and therapeutic lifestyle changes 总被引:2,自引:0,他引:2
Despite the large burden of cardiovascular disease on society, abnormal lipid levels, which are associated with an increase in coronary heart disease mortality, are not being adequately managed in many individuals. Poor patient compliance with therapeutic lifestyle changes and lipid-modifying therapies contribute to this treatment gap. If management of lipid levels is to reduce cardiovascular mortality effectively, poor compliance with treatment needs to be understood and addressed. Educating and motivating patients to understand the need for compliance with continued therapy is an important step for ensuring that the benefits of lipid management cited in clinical trials are translated to the general population. This will require a proactive approach from both patients and physicians. Well-tolerated and effective therapies may also help compliance by reducing the incidence of side effects and the need for complex dosing regimens. Suboptimal treatment of lipid levels is currently limiting the effectiveness of primary and secondary prevention of coronary heart disease; methods for improving compliance should be a key strategy to overcoming this problem. 相似文献
97.
Bloodspot cortisol, where finger pricked blood is applied to blotting paper, is suitable for repeated measurements in the home environment. The use of bloodspot cortisol measurements in children with asthma and the effect of inhaled corticosteroids on daytime cortisol concentrations were assessed. Twenty children with mild asthma were randomised to receive double blind either placebo or beclomethasone dipropionate 200 micrograms twice daily. Blood was taken by finger prick at home on waking, and treatment administered. Blood was then taken one hour after treatment, at lunchtime, and in the evening. The area under the curve (AUC) for the four time points was calculated as a composite index of daytime cortisol. Mean (SEM) bloodspot cortisols fell progressively over the day from 199.2 (15.6) nmol/l to 58.4 (8.9) nmol/l. Cortisol in the group treated with beclomethasone dipropionate was lower at all time points, but was significant only after treatment (mean (SEM) 120.9 (14.3) v 177.5 (21.0) nmol/l) and at lunchtime (mean (SEM) 82.7 (12.4) v 128.9 (12.6) nmol/l). AUC for the beclomethasone dipropionate treated group was also significantly decreased (mean (SEM) 317 (31.4) v 446 (29.7)). Beclomethasone dipropionate at a dose of 400 micrograms/day significantly suppresses the daytime cortisol profile. 相似文献
98.
99.
Production of an antiserum specific to rat brainl-glutamic acid decar?ylase is described, featuring the injection of an antigen-antibody complex. Partial purification of glutamate decar?ylase was first achieved through differential centrifugation, ammonium sulfate fractionation, chromatography on Sephadex G-150, preparative isoelectric focusing in sucrose gradient and polyacrylamide gel electrophoresis for the production of a preliminary polyvalent, so called ‘trapping’ glutamate decar?ylase antiserum in sheep. In rat brain homogenate supernatant this antiserum maximally inhibited glutamate decar?ylase activity by 80% and totally precipitated enzyme activity on centrifugation. This antiserum, however, was polyvalent, as in crossed immunoelectrophoresis it detected four antigens in rat brain homogenate supernatant and three antigens in a partially purified preparation of glutamate decar?ylase. One of these three precipitin lines could be radioactively labelled by 2-[3H]-γ-acetylenic γ-aminobutyrate, an irreversible inhibitor of glutamate decar?ylase. Injection of this antigen-antibody-precipitin line into a new non-immunized sheep yielded a new antiserum, which slightly inhibited but maximally precipitated 85% of the glutamate decar?ylase activity in rat brain homogenate supernatant. In crossed immunoelectrophoresis the latter antiserum detected one antigen in the partially purified preparation of glutamate decar?ylase. In crossed immunoelectrophoresis with intermediate gel the antiserum altered the mobility of a single antigen in brain homogenate supernatant.Thus, according to precipitating characteristics, the second antiserum appears to be specific to glutamate decar?ylase. 相似文献
100.
The clinical syndrome of striatal dopamine deficiency. Parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) 总被引:3,自引:0,他引:3
R S Burns P A LeWitt M H Ebert H Pakkenberg I J Kopin 《The New England journal of medicine》1985,312(22):1418-1421
Exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces a syndrome that resembles Parkinson's disease. To compare the biochemical abnormalities produced by this compound in human beings with those occurring in Parkinson's disease, we examined biogenic amine metabolites in cerebrospinal fluid and urine from six patients with MPTP-induced parkinsonism and eight patients with Parkinson's disease. In both forms of parkinsonism, the cerebrospinal fluid levels of homovanillic acid, the major metabolite of dopamine, were reduced, whereas the levels of the serotonin metabolite 5-hydroxyindoleacetic acid were normal. The cerebrospinal fluid levels of 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), the major metabolite of norepinephrine in the brain, after adjustment for plasma MHPG, were elevated (greater than 6.0 ng per milliliter) in MPTP-induced parkinsonism, whereas MHPG levels were reduced (less than 6.0) in Parkinson's disease. Neurons containing norepinephrine in the brain are involved in the degenerative process of Parkinson's disease, whereas they are spared in MPTP-induced parkinsonism. The selective destruction by MPTP of nigrostriatal dopamine neurons that is responsible for the movement disorder also appears to result in an increase in central noradrenergic activity, which is not possible in Parkinson's disease. Thus, differences in central noradrenergic activity, reflected in cerebrospinal fluid levels of MHPG, distinguish these two forms of parkinsonism. 相似文献