全文获取类型
收费全文 | 547篇 |
免费 | 30篇 |
国内免费 | 5篇 |
专业分类
儿科学 | 2篇 |
妇产科学 | 12篇 |
基础医学 | 77篇 |
口腔科学 | 1篇 |
临床医学 | 75篇 |
内科学 | 148篇 |
皮肤病学 | 6篇 |
神经病学 | 28篇 |
特种医学 | 38篇 |
外科学 | 60篇 |
综合类 | 4篇 |
预防医学 | 23篇 |
眼科学 | 10篇 |
药学 | 60篇 |
中国医学 | 4篇 |
肿瘤学 | 34篇 |
出版年
2023年 | 10篇 |
2022年 | 9篇 |
2021年 | 19篇 |
2020年 | 4篇 |
2019年 | 11篇 |
2018年 | 14篇 |
2017年 | 13篇 |
2016年 | 15篇 |
2015年 | 10篇 |
2014年 | 21篇 |
2013年 | 20篇 |
2012年 | 37篇 |
2011年 | 50篇 |
2010年 | 22篇 |
2009年 | 20篇 |
2008年 | 31篇 |
2007年 | 23篇 |
2006年 | 29篇 |
2005年 | 23篇 |
2004年 | 15篇 |
2003年 | 28篇 |
2002年 | 24篇 |
2001年 | 15篇 |
2000年 | 13篇 |
1999年 | 4篇 |
1998年 | 4篇 |
1997年 | 2篇 |
1996年 | 4篇 |
1995年 | 5篇 |
1994年 | 5篇 |
1993年 | 4篇 |
1992年 | 4篇 |
1991年 | 9篇 |
1990年 | 11篇 |
1989年 | 12篇 |
1988年 | 6篇 |
1987年 | 7篇 |
1986年 | 7篇 |
1985年 | 4篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1979年 | 2篇 |
1977年 | 1篇 |
1975年 | 1篇 |
1973年 | 3篇 |
1971年 | 1篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有582条查询结果,搜索用时 15 毫秒
1.
E Cereda A Ezhaya M Gil Quintero E Bellora E Dubini R Micheletti A Schiavone A Brambilla G B Schiavi A Donetti 《Journal of medicinal chemistry》1990,33(8):2108-2113
Amidines (guanidine, formamidine, and acetamidine) were introduced as substitutes for the cationic heads present in atropine, scopolamine, and corresponding quaternary derivatives. Amidine systems are intermediate in structure between tertiary amines and quaternary compounds, at least as regards ionization and electronic properties, but differ from the latter in shape (planar not tetrahedral). They have additional binding opportunities on account of their hydrogen-bond-forming capacity. The effect of the introduction of these cationic heads on the affinity for different muscarinic acetyl choline receptor (m-AcChR) subtypes was investigated in vitro, in binding displacement studies, and in functional tests on isolated organs. All new compounds (3a,b-5a,b) showed high affinity for the m-AcChR considered, comparable or slightly inferior to that of the parent drugs (1a-e). The new amidine derivatives proved effective as spasmolytic agents, with little tendency to cause central effects. However, no separation was achieved of spasmolytic and other untoward effects, like inhibition of salivation. Thus, amidine moieties are effective bioisosteric substitutes for conventional cationic heads present in antimuscarinic agents. Their unusual physical-chemical properties make them useful tools when modulation of pharmacokinetic or pharmacodynamic effects is required. 相似文献
2.
Markus Golling Cosima Jahnke Hamidreza Fonouni Rezvan Ahmadi Renate Urbaschek Raoul Breitkreutz Peter Schemmer Thomas W Kraus Martha M Gebhard Markus W Büchler Arianeb Mehrabi 《Liver transplantation》2007,13(4):607-617
The liver function and perfusion following brain death is mainly influenced by the sympathetic nerves and hormones. We examined the specific influence of surgical liver denervation on systemic and hepatic perfusion parameters, bowel ischemia and oxidative stress in hemodynamically stable BD and control (living donor [LD]) pigs. Brain death was induced in 8 pigs via saline infusion into the balloon of an epidural Tieman-catheter (1 mL/15 minutes) and compared to the control group (n = 6) over 4 hours. At 2 hours postoperatively, complete liver denervation was initiated. We analyzed systemic cardiocirculatory parameters (mean arterial pressure, aortic flow, bowel ischemia (endotoxin, and endotoxin-neutralizing capacity) and oxidative stress (total glutathione in erythrocytes [tGSH(E)]) and compared them to local/hepatic perfusion parameters (hepatic artery and portal venous flow, liver blood flow index, and microperfusion), local bowel ischemia (intramucosal pH [pHi] of stomach [pHi(S)]/colon[pHi(C)]), and liver oxidative stress (glutathione [rGSH(L), GSSG(L)]). Following brain death, the parameters including mean arterial pressure, aortic flow, pHi, endotoxin, and tGSH(E) showed no significant changes at 2 hours. Portal venous flow and microperfusion were decreased significantly and hepatic arterial buffer response was ineffective. Hepatic oxidative stress was increased in BD animals (decrease rGSH(L), increase GSSG(L)). Surgical denervation/manipulation increased portal venous flow significantly, hepatic arterial buffer response became effective, and stomach pHi decreased (BD and LD groups). Hepatic oxidative stress was reduced in the BD group (increase rGSH(L)/GSSG(L); P < 0.001) while it was increased in the LD group (decrease rGSH(L)/GSSG(L); P < 0.001). In conclusion, denervation reduces hepatic oxidative stress in BD only in contrast to the LD. The reciprocal effect of denervation depends on the state of neural activation and postulates a potential benefit of surgical denervation before organ harvesting in brain death. 相似文献
3.
A Sgalambro A Marras F Lombardi C Guasconi G Schiavone G Sportelli S Del Giudice C Marinoni 《Giornale italiano di cardiologia》1987,17(8):667-672
Tricuspid regurgitation (TR) is detected by Doppler echocardiography in a high proportion of patients with right ventricle pressure or volume overload. Continuous wave Doppler (CW) provides a noninvasive estimation of the transtricuspid systolic pressure gradient, applying the modified Bernoulli formula to the maximum velocity of the TR jet. The purpose of this study was to test the accuracy of the CW prediction of systolic right ventricular pressure (RVPs), obtained adding a clinical estimate of the mean right atrial pressure (RAPm) to the Doppler derived pressure gradient. The study population consisted of 22 adult patients with Doppler proved TR, undergoing right heart catheterization (cath) for mitral valve disease (12 pts), atrial septal defect (8 pts), dilated cardiomyopathy (1 pt) or pulmonary hypertension (1 pt). Two studies were duplicated after nifedipine administration. TR was graded by pulsed Doppler flow mapping as mild in 7, moderate in 11, severe in 4 pts. RAPm was estimated clinically from the inspection of neck veins pulsatility (mmHg = pulsatility cm+5/1.3). At CATH RVPs ranged from 27 to 80 (46 +/- 17) mmHg, RAPm from 0 to 13 (6 +/- 3) mmHg. RVPs Doppler prediction showed a close correlation with CATH (r .97, SEE 4.2 mmHg), with a slight mean underestimation (-2 +/- 4 mmHg) (Fig. 3, Tab. I). The discrepancies between CW and CATH ranged from -9 to +10 mmHg, almost entirely due to inaccuracy of the RAPm clinical estimate (r .48, see 3.8 mmHg) (Fig. 4, Tab. I).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
4.
5.
Inducible nitric oxide synthase expression in human colorectal cancer: correlation with tumor angiogenesis 总被引:15,自引:0,他引:15 下载免费PDF全文
Cianchi F Cortesini C Fantappiè O Messerini L Schiavone N Vannacci A Nistri S Sardi I Baroni G Marzocca C Perna F Mazzanti R Bechi P Masini E 《The American journal of pathology》2003,162(3):793-801
To investigate the potential involvement of the nitric oxide (NO) pathway in colorectal carcinogenesis, we correlated the expression and the activity of inducible nitric oxide synthase (iNOS) with the degree of tumor angiogenesis in human colorectal cancer. Tumor samples and adjacent normal mucosa were obtained from 46 surgical specimens. Immunohistochemical expression of iNOS, vascular endothelial growth factor (VEGF), and CD31 was analyzed on paraffin-embedded tissue sections. iNOS activity and cyclic GMP levels were assessed by specific biochemical assays. iNOS protein expression was determined by Western blot analysis. iNOS and VEGF mRNA levels were evaluated using Northern blot analysis. Both iNOS and VEGF expressions correlated significantly with intratumor microvessel density (r(s) = 0.31, P = 0.02 and r(s) = 0.67, P < 0.0001, respectively). A significant correlation was also found between iNOS and VEGF expression (P = 0.001). iNOS activity and cyclic GMP production were significantly higher in the cancer specimens than in the normal mucosa (P < 0.0001 and P < 0.0001, respectively), as well as in metastatic tumors than in nonmetastatic ones (P = 0.002 and P = 0.04, respectively). Western and Northern blot analyses confirmed the up-regulation of the iNOS protein and gene in the tumor specimens as compared with normal mucosa. NO seems to play a role in colorectal cancer growth by promoting tumor angiogenesis. 相似文献
6.
Down-regulation of nitric oxide synthase-2 and cyclooxygenase-2 pathways by p53 in squamous cell carcinoma 总被引:7,自引:0,他引:7 下载免费PDF全文
Gallo O Schiavone N Papucci L Sardi I Magnelli L Franchi A Masini E Capaccioli S 《The American journal of pathology》2003,163(2):723-732
The goal of this study was to analyze the correlation between inducible nitric oxide synthase (iNOS) and COX-2 activities and p53 gene status in head and neck squamous cell carcinomas (HNSCCs) in vivo and in vitro. In a series of 43 HNSCCs we observed an up-regulation of both iNOS and COX-2 pathways in tumor tissues and both activities were correlated each other (rs = 0.612 and P = 0.0002). We also found that p53-mutated HNSCCs (25 cases, 58.1%) showed higher levels of iNOS activity and cGMP in comparison with wild-type p53 tumors (18 cases, 41.9%) (P = 0.0005 and P = 0.01), as well as higher iNOS immunohistochemical expression (P = 0.03). Analogously, higher PgE2 levels were documented in p53-mutated HNSCCs when compared with wild-type p53 tumors (P = 0.015) and COX-2 protein expression was higher in p53-mutated HNSCCs (P = 0.007). A431 cancer cells expressing a p53 temperature-sensitive mutant showed an approximately 1.9- and 2.6-fold decrease in spontaneous NO(2-)/NO(3-) and PgE2 synthesis at permissive temperature, respectively, when compared with the same cells at nonpermissive temperature (P 相似文献
7.
F. Pagani A. Brambilla A. Schiavone A. Giachetti 《Naunyn-Schmiedeberg's archives of pharmacology》1985,329(1):45-49
Summary In the perfused stomach preparation of the anaesthetized rat the cholinergic agonists acetylcholine (ACh) and bethanechol stimulated gastric acid secretion. Both agonists produced similar maximal acid output (70 mol/15 min) when infused intravenously. However, bethanechol was more potent, eliciting half maximal stimulation at 1.98 mol/kg/h. Secretory responses to either agonist were antagonized in a dose related fashion by blockade of muscarinic receptors with atropine. In contrast, inhibition of nicotinic receptors with hexamethonium produced a striking potentiation of ACh stimulated secretion whilst the bethanechol elicited secretion remained unaffected. In the presence of full nicotinic receptor blockade the ACh response curve was shifted to the left sixfold, half maximal stimulation being produced at 1.79 mol/kg/h. Cimetidine partially inhibited the secretory responses elicited by either ACh or bethanechol while blockade of adrenoceptors ( and ) did not affect acid output induced by cholinergic agonists. Secretion elicited by ACh is interpreted as being the composite effect of prosecretory action and an inhibitory mechanism due to the activation of nicotinic receptors. Hexamethonium, through nicotinic receptor blockade, inhibits the restricting mechanism and thus reveals the full stimulatory action of ACh. 相似文献
8.
The use of antioxidant compounds in the treatment of first psychotic episode: Highlights from preclinical studies 下载免费PDF全文
Recent evidence highlighted a pathogenetic link between redox dysregulation and the early stages of psychosis. Indeed, an increasing number of studies have pointed toward an association between oxidative stress, both at central and peripheral levels, and first psychotic episode. Moreover, basal low antioxidant capacity has been shown to directly correlate with cognitive impairment in the early onset of psychosis. In this context, the possibility to use antioxidant compounds in first psychotic episode, especially as supplementation to antipsychotic therapy, has become the focus of numerous investigations on rodents with the aim to translate data on the possible effects of antioxidant therapies to large populations of patients, with a diagnosis of the first psychotic episode. In this review, we will discuss studies, published from January 1st, 2007 to July 31st, 2017, investigating the effects of antioxidant compounds on neuropathological alterations observed in different rodent models characterized by a cluster of psychotic‐like symptoms reminiscent of what observed in human first psychotic episode. A final focus on the effective possibility to directly translate data obtained on rodents to humans will be also provided. 相似文献
9.
Transcatheter arterial chemoembolization (TACE) in treatment of hepatocellular carcinoma 总被引:17,自引:0,他引:17
Barone M Ettorre GC Ladisa R Schiavariello M Santoro C Francioso G Vinciguerra V Francavilla A 《Hepato-gastroenterology》2003,50(49):183-187
BACKGROUND/AIMS: Substantial differences about the efficacy of transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma are reported in literature. This probably depends on the fact that in each single study, different patient selection criteria, type of epidemiological approach, end points adopted and kind of technical approach were used. This study aims to evaluate the efficacy of segmental transcatheter arterial chemoembolization in amelioring patient survival and to determine which patients might really benefit from this treatment. METHODOLOGY: To achieve our goals 193 consecutive patients (110 treated and 83 untreated) were studied. They were selected in the same period of time and matched as far as their demographic and clinical characteristics. RESULTS: Our results demonstrate that both in treated and control patients, Child class, alpha-fetoprotein and tumor diameter significantly influenced survival, resulting important prognostic factors. Transcatheter arterial chemoembolization significantly ameliorated survival in treated patients compared to controls (p < 0.0001). CONCLUSIONS: Transcatheter arterial chemoembolization significantly ameliorates survival in patients with hepatocellular carcinoma. However, the presence of large tumors producing high alpha-fetoprotein levels in patients with advanced Child class should discourage treatment. 相似文献
10.
Alessio Gasperetti MD Marco Schiavone MD Mauro Biffi MD Michela Casella MD PhD Paolo Compagnucci MD Gianfranco Mitacchione MD PhD Andrea Angeletti MD Julia Vogler MD Riccardo Proietti MD PhD Matteo Ziacchi MD Antonio Dello Russo MD PhD Andrea Natale MD Roland R. Tilz MD Giovanni B. Forleo MD PhD 《Journal of cardiovascular electrophysiology》2021,32(11):3035-3041