全文获取类型
收费全文 | 542篇 |
免费 | 28篇 |
国内免费 | 14篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 18篇 |
妇产科学 | 4篇 |
基础医学 | 33篇 |
口腔科学 | 59篇 |
临床医学 | 37篇 |
内科学 | 62篇 |
皮肤病学 | 3篇 |
神经病学 | 53篇 |
特种医学 | 14篇 |
外国民族医学 | 2篇 |
外科学 | 145篇 |
预防医学 | 8篇 |
眼科学 | 6篇 |
药学 | 117篇 |
肿瘤学 | 20篇 |
出版年
2023年 | 4篇 |
2022年 | 6篇 |
2021年 | 5篇 |
2020年 | 6篇 |
2019年 | 10篇 |
2018年 | 4篇 |
2016年 | 7篇 |
2015年 | 12篇 |
2014年 | 8篇 |
2013年 | 7篇 |
2012年 | 15篇 |
2011年 | 15篇 |
2010年 | 7篇 |
2009年 | 8篇 |
2008年 | 14篇 |
2007年 | 13篇 |
2006年 | 14篇 |
2005年 | 19篇 |
2004年 | 26篇 |
2003年 | 28篇 |
2002年 | 21篇 |
2001年 | 20篇 |
2000年 | 16篇 |
1999年 | 28篇 |
1998年 | 10篇 |
1997年 | 4篇 |
1996年 | 5篇 |
1995年 | 4篇 |
1993年 | 7篇 |
1992年 | 13篇 |
1991年 | 9篇 |
1990年 | 9篇 |
1989年 | 11篇 |
1988年 | 13篇 |
1987年 | 27篇 |
1986年 | 13篇 |
1985年 | 23篇 |
1984年 | 15篇 |
1983年 | 7篇 |
1980年 | 5篇 |
1979年 | 5篇 |
1977年 | 5篇 |
1976年 | 7篇 |
1974年 | 8篇 |
1972年 | 8篇 |
1971年 | 7篇 |
1970年 | 8篇 |
1969年 | 16篇 |
1968年 | 6篇 |
1967年 | 5篇 |
排序方式: 共有584条查询结果,搜索用时 31 毫秒
1.
2.
Ilari Paakkari 《Basic & clinical pharmacology & toxicology》1994,75(Z2):56-59
Abstract The availability of many new nonsteroidal anti-inflammatory drugs (NSAIDs) has increased the total consumption during the past 20 years. The cost of different NSAID brands varies considerably probably reflecting increased research and development costs rather than a true therapeutic benefit for the patient. The current therapeutic problem in the treatment of musculoskeletal conditons with NSAIDs is to make a balanced analysis between benefits, risks, and costs. Assessment of risks and benefits should focus on the large subgroup (about 40%) of elderly NSAID users over 60 years who clearly stand at increased risk of NSAID-induced gastrointestinal complications. In the treatment of osteoarthritis more trials are needed to compare NSAIDs with plain analgesics (e.g. paracetamol). 相似文献
3.
alpha 2-Adrenoceptor agonists decrease free 3-methoxy-4-hydroxyphenylglycol in rat cerebrospinal fluid 总被引:2,自引:0,他引:2
The effects of alpha 2-adrenoceptor agonists on the concentrations of monoamine metabolites in cisternal cerebrospinal fluid (CSF) of freely moving rats were determined. Clonidine and two new imidazole derivatives, detomidine and medetomidine, and diazepam (as a control substance) were administered in sedative doses and the concentrations of unconjugated 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in CSF were monitored for 48 h. The alpha 2-agonists caused a dose-dependent, statistically significant decrease in the concentration of MHPG in CSF compared to the concentration in animals treated with saline or diazepam. Detomidine caused a statistically significant increase in the concentration of 5-HIAA compared to control treatments. The present results demonstrate the usefulness of monitoring drug-induced alterations in central nervous system (CNS) noradrenergic activity by measuring free MHPG in repeatedly collected cisternal CSF samples from freely moving rats. The alpha 2-agonists reduced the concentration of MHPG in CSF, indicating a decreased release, metabolism and turnover of noradrenaline in the CNS. 相似文献
4.
Decreased expression of protectin (CD59) in gut epithelium in ulcerative colitis and Crohn's disease
Without adequate protection, the cells of the human body would be susceptible to destruction by the complement system. The main defense against complement lysis is a molecule called protectin (CD59) that is widely distributed in human tissues. Because the complement system has been suggested to be involved in the pathogenesis of inflammatory bowel diseases, we examined the expression of protectin in the colonic epithelium of patients with ulcerative colitis or Crohn's disease and controls. Colorectal specimens from 6 patients with ulcerative colitis, 8 patients with Crohn's disease, and 4 controls were obtained from surgical resections. Frozen sections of the specimens were immunostained for protectin using the Bric 229 monoclonal antibody. The expression of protectin was found to be decreased in the epithelium of patients with ulcerative colitis. In patients with Crohn's disease, the epithelial expression of protectin was decreased in diseased areas of gut while the expression did not significantly differ from that in controls in macroscopically normal areas. There was no difference in the expression of protectin on vascular endothelium, mononuclear cells, or smooth muscle. The reduction in epithelial expression of protectin in patients with ulcerative colitis or Crohn's disease may render epithelial cells vulnerable to complement lysis and lead to the destruction of gut epithelium as seen typically in these diseases. 相似文献
5.
C C Jansson K Pohjanoksa J Lang S Wurster J M Savola M Scheinin 《European journal of pharmacology》1999,374(1):137-146
Transfected Chinese hamster ovary cells expressing human alpha2A-, alpha2B- and alpha2C-adrenoceptor subtypes were used to monitor alpha2-adrenoceptor-stimulated GTP hydrolysis. Incubation with 100 microM (-)-adrenaline resulted in stimulation of pertussis toxin-sensitive GTPase by 380% after activation of the alpha2A-subtype, by 320% after activation of the alpha2B-subtype and by 110% after activation of the alpha2C-subtype. The agonists dexmedetomidine, UK14,304 (5-bromo-6-[2-imidazoline-2-ylamino]quinoxaline) and oxymetazoline showed subtype-dependent efficacy. Dexmedetomidine was a full agonist at the alpha2B-subtype and a partial agonist at the alpha2A- and the alpha2C-subtypes. UK14,304 was a full agonist at the alpha2A-subtype and a partial agonist at the other two. Oxymetazoline showed strong partial agonism at the alpha2B-subtype (63% of adrenaline), but did not significantly activate the alpha2A- and the alpha2C-subtypes. These results agreed with cAMP accumulation experiments carried out with cell lines endogenously expressing the alpha2A-subtype (human erythroleukemia, HEL) or the alpha2B-subtype (neuroblastoma-glioma, NG108-15). The GTPase assay may thus provide a valuable tool for the identification of subtype-selective alpha2-adrenoceptor agonists. 相似文献
6.
Wound healing in denervated rat groin skin flap 总被引:1,自引:0,他引:1
Ranne J Kalimo H Pyykkö K Scheinin M Aaltonen V Niinikoski J Laato M 《European surgical research. Europ?ische chirurgische Forschung. Recherches chirurgicales européennes》2000,32(3):197-202
The purpose of the present study was to investigate the effect of denervation on dermal wound healing in rat groin skin flaps for 1-10 weeks. The structural differences between wounds in normal and in denervated skin were investigated histologically using Herovici's staining. Pro alpha1(I) collagen mRNA levels were studied using Northern hybridization. Denervation and reinnervation of the skin flaps was demonstrated with quantitative noradrenaline determination and immunohistochemically using neurofilament and S-100 antibodies. Denervation of the skin did not seem to have any apparent effects on wound healing as assessed by light microscopy. There were no significant differences in pro alpha1(I) collagen mRNA levels either. The thin muscle layer underlying the skin was the only element that clearly responded to the denervation. 相似文献
7.
Janne L?hdesm?ki Jukka Sallinen Ewen MacDonald Mika Scheinin 《Neuropsychopharmacology》2004,29(7):1282-1293
Amphetamines are commonly used to treat attention-deficit hyperactivity disorder, but are also widely abused. They are employed in schizophrenia-related animal models as they disrupt the prepulse inhibition (PPI) of the acoustic startle response. The behavioral effects of amphetamines have mainly been attributed to changes in dopamine transmission, but they also involve increases in the synaptic concentrations of norepinephrine (NE). alpha2-Adrenoceptors (alpha2-ARs) regulate the excitability and transmitter release of brain monoaminergic neurons mainly as inhibitory presynaptic auto- and heteroreceptors. Modulation of acoustic startle and its PPI by the alpha2A-AR subtype was investigated with mice lacking the alpha2A-AR (alpha2A-KO) and their wild-type (WT) controls, without drugs and after administration of the alpha2-AR agonist dexmedetomidine or the antagonist atipamezole. The interaction of D-amphetamine (D-amph) and the alpha2-AR-noradrenergic neuronal system in modulating startle reactivity and in regulating brain monoamine metabolism was assessed as the behavioral and neurochemical responses to D-amph alone, or to the combination of D-amph and dexmedetomidine or atipamezole. alpha2A-KO mice were supersensitive to both neurochemical and behavioral effects of D-amph. Brain NE stores of alpha2A-KO mice were depleted by D-amph, revealing the alpha2A-AR as essential in modulating the actions of D-amph. Also, increased startle responses and more pronounced disruption of PPI were noted in D-amph-treated alpha2A-KO mice. alpha2A-AR also appeared to be responsible for the startle-modulating effects of alpha2-AR drugs, since the startle attenuation after the alpha2-AR agonist dexmedetomidine was absent in alpha2A-KO mice, and the alpha2-AR antagonist atipamezole had opposite effects on the startle reflex in alpha2A-KO and WT mice. 相似文献
8.
Saila Antila Ullamari Pesonen Lasse Lehtonen Pasi Tapanainen Hanna Nikkanen Katja Vaahtera Harry Scheinin 《European journal of pharmaceutical sciences》2004,23(3):213-222
OBJECTIVE: The purpose of this study was to investigate the pharmacokinetics of levosimendan and to determine the primary pharmacokinetic parameters of the pharmacologically active metabolite OR-1896 in rapid and slow acetylators. METHODS: Levosimendan was administered as a constant rate (0.1 microg/(kg min)) i.v. infusion for 24h in six rapid and six slow acetylators based on N-acetyltransferase 2 genotyping. At the end of the infusion, a small amount (2.5 microg/kg) of (13)C-labeled OR-1896 was administered by i.v. infusion for 10 min. Blood samples were taken at predefined sampling points 14 days post-infusion and levosimendan and its metabolite concentrations were determined by LC-MS/MS. RESULTS: Steady-state concentrations of levosimendan were achieved within 4-8h and no differences were found in the pharmacokinetics of the parent compound between the rapid and slow acetylators. The maximum concentrations of amino phenylpyridazinone metabolite OR-1855 and N-acetylated conjugate OR-1896 were observed approximately 24h after terminating the infusion. AUC of OR-1896 was approximately 3.5 times higher in the rapid acetylators compared to the slow acetylators (P = 0.002, 95% confidence interval for group ratio from 2.0 to 8.2). The mean +/- S.D. fraction of levosimendan metabolized to OR-1896 was 6.8 +/- 2.8% in the rapid and 4.3 +/- 2.4% in the slow acetylators (P = 0.12). (13)C-OR-1855 concentrations were detected in plasma after administration of (13)C-OR-1896 indicating deacetylation from OR-1896 to OR-1855. CONCLUSIONS: Plasma OR-1896 levels during and after levosimendan treatment are dependent on the acetylation status of the subject-rapid acetylators having 3.5 times higher concentrations than slow acetylators. 相似文献
9.
Monica Terenziani MD Paolo D'Angelo MD Gianni Bisogno MD Renata Boldrini MD Giovanni Cecchetto MD Paola Collini MD Massimo Conte MD Tina De Laurentis MD Ilaria Ilari MD Paolo Indolfi MD Alessandro Inserra MD Luigi Piva MD Fortunato Siracusa MD Filippo Spreafico MD Paolo Tamaro MD Margherita Lo Curto MD 《Pediatric blood & cancer》2010,54(4):532-537
10.
Serum vitamin B12 concentration after proximal gastric vagotomy 总被引:1,自引:0,他引:1
H Paimela J Ahonen K H?ckerstedt T M Scheinin 《Scandinavian journal of gastroenterology》1984,19(3):445-448
The serum concentration of vitamin B12, blood hemoglobin, and gastric acid secretion capacity was studied preoperatively and 1 and 5 years after proximal gastric vagotomy (PGV) in 15 patients. There was a significant reduction in the mean concentration of vitamin B12 at 1 year, but this disappeared within 5 years after PGV. The serum concentration of vitamin B12, however, remained at all times within the health-related reference interval. The blood hemoglobin concentration was unaltered during the follow-up period. The decrease in gastric acid secretion capacity gained by PGV was permanent, and no tendency to increased acidity was observed during the 5-year period. The temporary decrease in serum concentration of vitamin B12 reflects a PGV-induced diminished production of intrinsic factor in the parietal cells. In the characterization of parietal cell function the determination of serum vitamin B12 concentration is, however, much less sensitive than gastric acid secretion tests. The observed change in vitamin B12 concentration after PGV was subclinical, self-corrected, and thus required no treatment. 相似文献