全文获取类型
收费全文 | 303篇 |
免费 | 17篇 |
专业分类
耳鼻咽喉 | 5篇 |
儿科学 | 13篇 |
妇产科学 | 19篇 |
基础医学 | 45篇 |
口腔科学 | 2篇 |
临床医学 | 19篇 |
内科学 | 52篇 |
皮肤病学 | 11篇 |
神经病学 | 35篇 |
特种医学 | 46篇 |
外科学 | 22篇 |
综合类 | 2篇 |
预防医学 | 21篇 |
眼科学 | 3篇 |
药学 | 9篇 |
肿瘤学 | 16篇 |
出版年
2024年 | 2篇 |
2023年 | 5篇 |
2022年 | 7篇 |
2021年 | 14篇 |
2020年 | 16篇 |
2019年 | 13篇 |
2018年 | 23篇 |
2017年 | 21篇 |
2016年 | 9篇 |
2015年 | 7篇 |
2014年 | 9篇 |
2013年 | 11篇 |
2012年 | 27篇 |
2011年 | 27篇 |
2010年 | 8篇 |
2009年 | 10篇 |
2008年 | 18篇 |
2007年 | 13篇 |
2006年 | 12篇 |
2005年 | 5篇 |
2004年 | 6篇 |
2003年 | 13篇 |
2002年 | 11篇 |
2001年 | 1篇 |
1999年 | 1篇 |
1997年 | 1篇 |
1996年 | 4篇 |
1995年 | 1篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1984年 | 1篇 |
1928年 | 1篇 |
1927年 | 1篇 |
1926年 | 2篇 |
1925年 | 2篇 |
1924年 | 5篇 |
1923年 | 1篇 |
1909年 | 1篇 |
1907年 | 2篇 |
1906年 | 4篇 |
1905年 | 1篇 |
排序方式: 共有320条查询结果,搜索用时 15 毫秒
1.
Roland Seifert Rahel Burde Günter Schultz 《Naunyn-Schmiedeberg's archives of pharmacology》1989,340(1):101-106
Summary There are controversial reports in the literature concerning the effects of opioids on superoxide (O
2
–
) formation in phagocytes, these agents being either inhibitory or stimulatory. We re-examined this issue and compared the effects of the Chemotactic peptide, N-formyl-l,-methionyl-l-leucyl-l-phenylalanine (fMet-Leu-Phe), phorbol myristate acetate (PMA), ATP, platelet activating factor (PAF), cytochalasin B (CB) and prostaglandin E1 (PGE1) with those of various opioids on O
2
–
formation in human neutrophils and HL-60 leukemic cells under defined experimental conditions. In the presence of CB, fMet-Leu-Phe and PAF concentration-dependently activated O
2
–
formation in neutrophils with EC50 values of 20 nM and 100 nM, respectively. In the absence of CB, fMet-Leu-Phe and PAF were much less effective. PAF synergistically enhanced O
2
–
formation induced by fMet-Leu-Phe. ATP at a concentration of 100 M and the opioids, methionine enkephalin, -endorphin, dynorphin, [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin, [d-Ala2-d-Leu5]-enkephalin and morphine at concentrations between 10 pM to 1 M did not activate O
2
–
formation. ATP but not \-endorphin potentiated fMet-Leu-Phe-induced O
2
–
formation. O
2
–
formation induced by a maximally stimulatory concentration of PMA (100 ng/ml) was enhanced by fMet-Leu-Phe but was unaffected by methionine enkephalin or PGE1. PMA at a non-stimulatory concentration (2 ng/ml) potentiated the effect of fMet-Leu-Phe but did not induce responsiveness to PAF, ATP or -endorphin. PGE1 strongly inhibited fMet-Leu-Phe-induced O
2
–
formation, whereas morphine, methionine enkephalin and the opioid antagonist, naloxone, were without effect. In HL-60 cells differentiated with dibutyryl cAMP, fMet-Leu-Phe, PAF and ATP but not -endorphin activated O
2
–
formation. Our results show that O
2
–
formation is differentially regulated by various classes of intercellular signal molecules and that opioids do not play a role in the regulation of O
2
–
formation. The precise definition of the experimental conditions and control experiments with established modulators of O
2
–
formation are essential to evaluate the role of opioids in the regulation of this effector system.Send offprint requests to R. Seifert at the above address 相似文献
2.
Many tumor cells are resistant to tumor necrosis factor alpha (TNFalpha)-induced apoptosis. Adenovirus early region 1A (AdE1A) sensitizes the otherwise resistant cells to TNFalpha. AdE1A also stabilizes the p53 protein. The present study demonstrates a correlation between AdE1A-induced sensitization and stabilization of p53 in TNFalpha-induced apoptosis since the N-terminal and CR2 regions, the binding sites for CBP/p300, Rb and 26S proteasome regulatory components, are required for both these actions of AdE1A. TNFalpha does not induce apoptosis and AdE1A fails to sensitize TNFalpha cytotoxicity in p53-negative cells. However, introduction of exogenous p53 overcomes the cellular resistance to TNFalpha toxicity and enhances AdE1A sensitization, demonstrating that AdE1A sensitizes TNFalpha-induced apoptosis by its stabilization of p53. A proteasome inhibitor, lactacystin, enhances TNFalpha cytotoxicity in p53-positive and -negative cells, suggesting that accumulation of cellular proteins other than p53 might also regulate the cellular response to TNFalpha signaling. 相似文献
3.
Astrid Hagelüken Rahel Burde Bernd Nürnberg Rainer Harhammer Armin Buschauer Roland Seifert 《Naunyn-Schmiedeberg's archives of pharmacology》1995,351(3):305-308
Formyl peptides activate superoxide anion (O2
–) formation in human neutrophils and in HL-60 cells via pertussis toxin (PTX)-sensitive guanine nucleotide-binding proteins (G-proteins), and histamine (HA) mediates inhibition of O2
– formation via H2-receptors. We have studied the effects of lipophilic arpromidine-derived guanidines, which are potent, full H2-receptor agonists in the guinea pig atrium, on O2
– formation and on activation of G-proteins in HL-60 membranes and on purified G-proteins. We have also studied the effects of a HA trifluoromethyl-toluidide derivative (HTMT), a cationic-amphiphilic HA derivative which activates O2
– formation in HL-60 cells through a mechanism which is independent of known HA receptor subtypes, on G-protein activation. Guanidines, at concentrations, up to 30 mol/l inhibited and, at concentrations above 30 mol/l, enhanced formyl peptide-induce O2
– formation in neutrophils. In HL-60 cells, guanidines per se activated O2
– formation. The stimulatory effects of guanidines on O2
– formation were not inhibited by H1- or H2-receptor antagonists. In HL-60 membranes, guanidines and HTMT, activated high-affinity GTPase in a PTX-sensitive manner. These substances also increased GTP hydrolysis effected by transducin and Gi/Go-proteins. Our data suggest that lipophilic guanidines and HTMT may act as receptor-independent activators of PTX-sensitive G-proteins, resulting in stimulation of O
2
–
formation. 相似文献
4.
Stenting for restenotic lesions with the BARD XT stent 总被引:1,自引:0,他引:1
Rahel BM Suttorp MJ Te Riele HA Bal ET Ernst SM Mast EG Ten Berg JM Kelder JC Plokker HW 《Journal of interventional cardiology》2003,16(3):227-230
BACKGROUND: Conventional PTCA for the treatment of restenotic lesions is associated with a high rate of recurrence (30-50%). Primary stenting decreases the restenosis rate at long-term follow-up. METHODS: One-hundred consecutive patients with restenosis received a Bard XT stent. Follow-up angiography was performed after 6 months. Angiograms were compared by means of computed quantitative analysis. RESULTS: The mean pretreatment reference diameter was 2.88 +/- 0.51 mm. The mean minimal luminal diameter (MLD) increased from 1.09 +/- 0.57 mm to 2.70 +/- 0.44 mm. The percent diameter stenosis decreased from 66 +/- 13% to 15 +/- 10%. The procedural success rate was 99%. At 6 month follow-up repeat angiography was performed in 86 patients. The mean MLD was 1.74 +/- 0.67 mm with a mean diameter stenosis of 41 +/- 20%. Residual anginal complaints were reported in 29% of patients. In-stent restenosis (defined as diameter stenosis of more than 50%) occurred in 18% of the patients. CONCLUSION: Placement of the Bard XT stent in restenotic lesions is feasible, has an excellent short term outcome and yields a favorable result at 6 month follow-up angiography. 相似文献
5.
Rahel BM Suttorp MJ ten Berg JM Bal ET Ernst SM Rensing BJ Kelder JC Plokker HW 《Journal of interventional cardiology》2004,17(4):197-201
INTRODUCTION: Conventional percutaneous coronary intervention for the treatment of in-stent restenosis (ISR) has shown a high rate of ISR (30-55%). Considering the need for both extrusion of hyperplastic intima and additional stent expansion, a cutting balloon might be more effective for the treatment of ISR. METHODS: We prospectively assessed the immediate and 8-month outcome of balloon angioplasty using the Barath Cutting Balloon in 100 consecutive patients (mean age: 60.5 +/- 10.8 years, 71% male). RESULTS: In 73 lesions (73%), a good result was reached with the cutting balloon only. In 21 lesions (21%) postdilatation and in 6 lesions (6%) predilatation with a conventional balloon was necessary. The mean inflation pressure was 8.7 +/- 2.0 (range: 6.0-18.0) atm. Before the procedure the mean minimal luminal diameter (MLD) was 0.95 +/- 0.45 mm. Quantitative coronary analysis showed a mean diameter stenosis of 65%+/- 16%. Immediately after the procedure the mean MLD was 2.42 +/- 0.54 mm with a mean diameter stenosis of 19%+/- 13%. Two patients died during the follow-up period (1 stroke, 1 nonvascular). At 8-month follow-up 26 patients (26%) reported to have anginal complaints CCS class II-IV of whom 16 (16%) needed target lesion revascularization. CONCLUSION: Treatment of ISR using the Barath Cutting Balloon can be performed safely with good immediate results and a relatively low need for repeated target lesion revascularization at 8-month follow-up. 相似文献
6.
Wolfgang Hasemann Florian F. Grossmann Rahel Stadler Roland Bingisser Dieter Breil Martina Hafner Reto W. Kressig Christian H. Nickel 《Internal and emergency medicine》2018,13(6):915-922
Delirium is frequent in older Emergency Department (ED) patients, but detection rates for delirium in the ED are low. To aid in identifying delirium, we developed and implemented a two-step systematic delirium screening and assessment tool in our ED: the modified Confusion Assessment Method for the Emergency Department (mCAM-ED). Components of the mCAM-ED include: (1) screening for inattention, the main feature of delirium, which was performed with the Months Backwards Test (MBT); (2) delirium assessment based on a structured interview with questions from the Mental Status Questionnaire by Kahn et al. and the Comprehension Test by Hart et al. The aims of our study are (1) to investigate the performance criteria of the mCAM-ED tool in a consecutive sample of older ED patients, (2) to evaluate the performance of the mCAM-ED in patients with and without dementia and (3) to test whether this tool is efficient in keeping evaluation time to a minimum and reducing screening and assessment burden on the patient. For this prospective validation study, we recruited a consecutive sample of ED patients aged 65 and older during an 11-day period in November 2015. Trained nurses assessed patients with the mCAM-ED. Results were compared to the reference standard [i.e. the geriatricians’ delirium diagnosis based on the criteria of the Text Revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR)]. Performance criteria were computed. We included 286 consecutive ED patients aged 65 and older. The median age was 80.02 (Q1 = 72.15; Q3 = 86.76), 58.7% of included patients were female, 14.3% had dementia. We found a delirium prevalence of 7.0%. In patients with dementia, specificity and positive likelihood ratio were lower. When compared to the reference standard, delirium assessment with the mCAM-ED has a 0.98 specificity and a 39.9 positive likelihood ratio. In 80.0% of all cases, the first step of the mCAM-ED, i.e. screening for inattention with the MBT, took less than 30 s. On average, the complete mCAM-ED assessment required 3.2 (SD 2.0), 5.6 (SD 3.2), and 6.2 (SD 2.3) minutes in cognitively unimpaired patients, patients with dementia and patients with dementia or delirium, respectively. The mCAM-ED is able to efficiently rule out delirium as well as confirm the diagnosis of delirium in elderly patients with and without dementia and applies minimal screening and assessment burden on the patient. 相似文献
7.
Froehlich-Zahnd R George JN Vesely SK Terrell DR Aboulfatova K Dong JF Luken BM Voorberg J Budde U Sulzer I Lämmle B Kremer Hovinga JA 《Haematologica》2012,97(2):297-303
Background
Severe ADAMTS13 deficiency is a critical component of the pathogenesis of idiopathic thrombotic thrombocytopenic purpura but is found only in about 60% of patients clinically diagnosed with this disease.Design and Methods
Over a period of 8 years and six episodes of thrombotic thrombocytopenic purpura we studied the evolution of the anti-ADAMTS13 antibody response in a patient using different ADAMTS13 assays and epitope mapping.Results
Anti-ADAMTS13 autoantibodies were found in all episodes but were inhibitory only in the last two episodes. In a flow-based assay, normal ADAMTS13 activity was found only during the first disease episode, while ADAMTS13 activity was normal using a static assay in episodes 1 and 3, and severely deficient in the last two episodes. Fluorescence evolution in a modified fluorescence resonance energy transfer assay using a von Willebrand factor A2 domain peptide substrate was linear in episodes 1, 5 and 6, but increased exponentially in episodes 3 and 4. Despite the variable functional characteristics of the anti-ADAMTS13 autoantibodies, their principal epitope was the ADAMTS13 spacer domain in all episodes.Conclusions
The patient is unique as he displayed features of maturation or shaping of the anti-ADAMTS13 autoantibody response during the course of multiple episodes of thrombotic thrombocytopenic purpura. Anti-ADAMTS13 autoantibodies may be important in vivo despite normal ADAMTS13 activity in routine assays. Consequently, treatment decisions should not be based solely on activity assay results. 相似文献8.
Rahel Gerig Barbara Ernst Britta Wilms Martin Thurnheer Bernd Schultes 《Obesity surgery》2013,23(5):698-702
Severely obese subjects have been found to show a high prevalence of distinct nutritional deficiencies even without any bariatric intervention but the underlying reasons remain obscure. We tested the hypothesis that gastric Helicobacter pylori infection is associated with increased nutritional deficiency rates. Taking advantage of our large database, we identified 404 patients who had undergone a gastroscopy—as a standard diagnostic assessment before bariatric surgery—along with a histological examination of gastric mucosal biopsies with concurrent nutritional blood measurements. Eighty-five (21 %) of the obese patients included in the study displayed a gastric H. pylori infection. Sex distribution, age and body mass index did not differ between H. pylori+ and H. pylori? patients (P?>?0.29). Referring to nutritional markers, neither serum levels of total protein, albumin, calcium, phosphate, magnesium, ferritin, zinc, copper, vitamin B12, folate and 25-OH vitamin D3 nor respective deficiency rates differed between the H. pylori+ and H. pylori? patients group (all P?>?0.13). Overall, 49.5 % of the bariatric candidates displayed at least one nutritional deficiency. Our data confirm previous reports on high prevalences of nutritional deficiencies in severely obese subjects. However, they do not provide evidence for a contributing role of gastric H. pylori infection to these nutritional alterations. 相似文献
9.
Rahel Meier Regula Marthy Christoph H. Saely Markus S. Kuster Karlmeinrad Giesinger Hans Rickli 《European journal of orthopaedic surgery & traumatology : orthopedie traumatologie》2016,26(8):921-928
Introduction
Preoperative discontinuation of aspirin (acetylsalicylic acid) can reduce bleeding risk but may increase the risk of perioperative cardiovascular events.Materials and methods
We retrospectively assessed the impact of preoperative continuation versus discontinuation of aspirin compared with a control group in a cohort of 739 consecutive patients undergoing total hip (THA) (n = 396) or knee arthroplasty (TKA) (n = 343) at a tertiary hospital. Bleeding risk, local complications, orthopaedic outcome, and cardiac and cerebral complications were assessed.Results
Four hundred and sixty-five patients did not receive antithrombotic or full-dose anticoagulant medication, 175 patients were taking low-dose aspirin, 99 vitamin K antagonists, clopidogrel, or a combination of these drugs. Of the patients taking aspirin, 139 discontinued and 36 continued aspirin. Blood loss and local bleeding complications were comparable in these two groups. TKA patients who continued aspirin more frequently showed marked knee swelling after 1 week than those discontinuing aspirin (35.1 vs. 81.3 %; p = 0.001). However, orthopaedic outcome did not differ significantly between the two groups. There was a trend towards an increased risk of cardiac complications in patients who discontinued aspirin (6.5 vs. 0.0 %; p = 0.107).Conclusions
Continuation or discontinuation of aspirin did not show a statistically significant difference in the risk of relevant perioperative bleeding complications in our study. Continuation of aspirin was associated with a transitory increase in knee swelling, but had no effect on orthopaedic outcome. Continuation of aspirin may be associated with a favourable perioperative cardiac outcome. Our data support perioperative continuation of aspirin intake in patients undergoing THA or TKA.10.