全文获取类型
收费全文 | 1423篇 |
免费 | 73篇 |
国内免费 | 8篇 |
专业分类
耳鼻咽喉 | 27篇 |
儿科学 | 37篇 |
妇产科学 | 31篇 |
基础医学 | 142篇 |
口腔科学 | 29篇 |
临床医学 | 150篇 |
内科学 | 257篇 |
皮肤病学 | 17篇 |
神经病学 | 115篇 |
特种医学 | 100篇 |
外科学 | 292篇 |
综合类 | 14篇 |
预防医学 | 49篇 |
眼科学 | 41篇 |
药学 | 155篇 |
中国医学 | 7篇 |
肿瘤学 | 41篇 |
出版年
2023年 | 19篇 |
2022年 | 7篇 |
2021年 | 80篇 |
2020年 | 39篇 |
2019年 | 44篇 |
2018年 | 63篇 |
2017年 | 50篇 |
2016年 | 42篇 |
2015年 | 45篇 |
2014年 | 68篇 |
2013年 | 88篇 |
2012年 | 97篇 |
2011年 | 103篇 |
2010年 | 61篇 |
2009年 | 54篇 |
2008年 | 65篇 |
2007年 | 94篇 |
2006年 | 115篇 |
2005年 | 72篇 |
2004年 | 76篇 |
2003年 | 57篇 |
2002年 | 72篇 |
2001年 | 5篇 |
2000年 | 15篇 |
1999年 | 7篇 |
1998年 | 11篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1995年 | 4篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1992年 | 5篇 |
1991年 | 9篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1966年 | 1篇 |
1965年 | 2篇 |
1960年 | 1篇 |
排序方式: 共有1504条查询结果,搜索用时 15 毫秒
1.
Kamil Kuca Kamil Musilek Daniel Jun Eugenie Nepovimova Ondrej Soukup Jan Korabecny 《Toxin reviews》2020,39(2):157-166
AbstractOxime K074 was formerly considered to be a lead structure for design of novel oximes for reactivation of tabun-inhibited acetylcholinesterase (AChE). In this study, we are summarizing its reactivation activity in case of other nerve agents (sarin, cyclosarin, VX and Russian VX) and pesticides (chlorpyrifos, methylchlorpyrifos and DDVP). For this purpose, standard in vitro method using rat brain homogenate was used. As resulted, oxime K074 was able to reactivate brain ChE (cholinesterases) inhibited by all used nerve agents and pesticides excluding cyclosarin-inhibited ChE. Only slight modification in structure of sarin (isopropyl moiety) and cyclosarin (cyclohexyl moiety) caused extraordinary differences in the reactivation of acetylcholinesterase inhibited by these nerve agents. Obtained molecular docking results suggest that the oxime K074 interacts very well with the inhibitors addressed in this work, and the data obtained by the QM/MM approach showed a good correlation with our experimental results of reactivation rate (%) by the oxime K074. 相似文献
2.
Irina V. Poddubnaya Sergey M. Alekseev Kamil D. Kaplanov Les M. Lukavetskyy Grigoriy B. Rekhtman Tuphan K. Dolai V. Satya Suresh Attili Carlos D. Bermúdez Aleksandr A. Isaev Ekaterina V. Chernyaeva Roman A. Ivanov 《Hematological oncology》2020,38(1):67-73
BCD-020 is a proposed rituximab biosimilar, which has shown high similarity to rituximab in quality and nonclinical studies in vitro and in vivo. International multicenter clinical trial was conducted to compare efficacy and safety of BCD-020 and reference rituximab in adult (older than 18 years) patients with indolent lymphomas (follicular lymphoma grade 1-2, splenic marginal zone lymphoma, and nodal marginal zone lymphoma). Pharmacokinetics, pharmacodynamics, and immunogenicity were also studied. Patients with no previous biologic treatment for lymphoma were randomly assigned 1:1 to receive BCD-020 or comparator 375 mg/m2 for 4 weeks. Primary study outcome was day 50 overall response rate defined as complete or partial remission. Equivalence range was −20% to 20% for 95% CI for overall response rates difference. Secondary outcomes included adverse events, pharmacokinetics, pharmacodynamics, and immunogenicity. One hundred seventy-four patients were enrolled, 89 in BCD-020 arm and 85 in comparator arm. The overall response rate was 44.71% in BCD-020 arm and 41.89% in comparator arm. Limits of 95% confidence interval (CI) for difference of overall response rates between arms were (−12.62%-18.24%) showing equivalent efficacy. Sixty-one (68.54%) and 59 (69.41%) patients had at least one adverse event in BCD-020 arm or comparator arm, respectively. No unexpected adverse reactions were reported. Antidrug antibodies with no neutralizing activity were detected in two patients in comparator arm on day 14 further declining below detection threshold. Rituximab concentrations had equivalent pattern after intravenous administration of both drugs. Both drugs caused depletion of B-cells without significant influence on other blood cell lineages. In this study, we showed equivalent efficacy of BCD-020 and reference rituximab when used in patients with CD20-positive indolent lymphomas. We also confirmed pharmacokinetic equivalence of BCD-020 and reference rituximab. Safety profile, pharmacodynamics, and immunogenicity of BCD-020 were also comparable with those of reference rituximab. 相似文献
3.
Burin Karsl Kamil nce Nevzat Gnder Bahri Bozgeyik Volkan Klnolu 《Indian Journal of Orthopaedics》2021,55(3):688
BackgroundThe coexistence of supracondylar humerus fracture and forearm fracture is a rare trauma (3–13%) and it is called floating elbow. The aim of this study is to clinically compare the treatment outcomes of the patients diagnosed with floating elbow who underwent surgical treatment and who were followed up forearm with immobilization with splint.Materials and MethodsWhen scanned retrospectively, 60 patients who were treated with the diagnosis of floating elbow due to traumatic causes and followed up for at least 1 year were included in our study. Surgical treatment was performed on 42 patients for forearm fracture. Eighteen patients followed up with immobilization with a long arm splint. The results were evaluated according to the criteria modified by Templeton and Graham, in comparison with the patient’s intact side.ResultsIn the patients whose forearms were followed up conservatively, the mean age was 5.67 ± 2.25 years, and the mean follow-up period was 62.17 ± 45.91 months. In the patients who underwent surgery for the forearm, the mean age was 8.79 ± 2.01 years, and the mean follow-up was 47.14 ± 34.25 months. Eighteen patients whose forearms followed up conservatively, 12 had excellent and good clinical results and 6 had poor and moderate clinical results. Excellent and good clinical results in 27 patients who underwent surgical treatment for their forearms, moderate and poor clinical results obtained in 15 of them. There was no significant difference between the two groups (p = 0.357).ConclusionsIn conclusion, satisfactory clinical and radiological outcomes can be obtained with immobilization of the forearm fracture with splint, if acceptable reduction can be provided for the forearm following fixation of the supracondylar humerus fracture with the K-wire for treatment of floating elbow injury. 相似文献
4.
A Comparison of the Reactivating and Therapeutic Efficacy of Two Newly Developed Oximes (K727 and K733) with Oxime K203 and Trimedoxime in Tabun‐Poisoned Rats and Mice 下载免费PDF全文
Jiri Kassa Vendula Sepsova Martina Tumova Anna Horova Kamil Musilek 《Basic & clinical pharmacology & toxicology》2015,116(4):367-371
The reactivating and therapeutic efficacy of three original bispyridinium oximes (K727, K733 and K203) and one currently available oxime (trimedoxime) was evaluated in tabun‐poisoned rats and mice. The oxime‐induced reactivation of tabun‐inhibited acetylcholinesterase was measured in diaphragm and brain of tabun‐poisoned rats. The results showed that the reactivating efficacy of two recently developed oximes (K727 and K733) does not achieve the level of the reactivation of tabun‐inhibited acetylcholinesterase induced by oxime K203 and trimedoxime. While all oximes studied were able to increase the activity of tabun‐inhibited acetylcholinesterase in diaphragm, oxime K733 was not able to reactivate tabun‐inhibited acetylcholinesterase in the brain. The therapeutic efficacy of all oximes studied roughly corresponds to their reactivating efficacy. While both recently developed oximes were able to reduce acute toxicity of tabun less than 1.5‐fold, another original oxime K203 and commonly used trimedoxime reduced the acute toxicity of tabun almost two times. In conclusion, the reactivating and therapeutic potency of both newly developed oximes does not prevail the effectiveness of oxime K203 and trimedoxime, and therefore, they are not suitable for their replacement of commonly used oximes for the antidotal treatment of acute tabun poisoning. 相似文献
5.
Karolina Stożek Kamil Grubczak Viviana Marolda Andrzej Eljaszewicz Marcin Moniuszko 《Autoimmunity》2020,53(1):46-55
AbstractIntroduction: As it is generally known, regulatory B cells (Bregs) control inflammation and autoimmunity. The significance of Bregs in the population of children with autoimmune thyroid diseases (AITD) still offers plenty of potential to explore. The aim of this study was to estimate the expression of Bregs (phenotype CD19+CD24+CD27+IL-10+, CD19+IL-10+, CD1d+CD5+CD19+IL-10+ and CD1d+CD5+CD19+CD24+CD27+) in a paediatric cohort with AITD and in health controls.Materials and methods: A total of 100 blood samples were obtained from 53 paediatric patients with Graves’ disease (GD) (N?=?12 newly diagnosed, mean age 12.5?±?3.5 and N?=?17 during methimazole therapy, mean age 12.7?±?4.4), Hashimoto’s thyroiditis (HT) (N?=?10 newly diagnosed, mean age 13.3?±?2.9 and N?=?10 during L-thyroxine therapy, mean age 13.7?±?3.4) and compared with healthy controls (C) (N?=?15, mean age 13.1?±?3.1). The expressions of the immune cell populations were analysed by four-color flow cytometry using a FASC Canto II cytometer (BD Biosciences).Results: There was a decreasing tendency in the number of lymphocytes B producing IL-10 (B10) cells among all B lymphocytes and more widely, also among all lymphocytes, in each study group, as compared to C. We reported a reduction in IL-10 production in Bregs with the expression of CD19+CD24+CD27+IL-10 and CD1d+CD5+CD19+IL-10+ in both untreated and treated AITD.Conclusions: Our data demonstrate that the reduction in the number of Bregs with CD19+CD24+CD27+IL-10+ and CD19+IL-10+ expression could be responsible for breaking immune tolerance and for AITD development in children. 相似文献
6.
Maria Arshad Muhammad Qaiser Fatmi Kamil Musilek Alamdar Hussain Kamil Kuca Georg Petroianu 《Toxicology mechanisms and methods》2018,28(1):62-68
Organophosphate (OP) poisoning is a major global health issue; while compounds from this group have been used intensively over the last century, an effective antidote is still lacking. Oxime-type acetylcholinesterase (AChE) reactivators are used to reactivate the OP inhibited AChE. Pralidoxime is the only US Food and Drug Administration approved oxime for therapeutic use but its efficacy has been disappointing. Two novel oximes (K378 and K727) were investigated in silico and in vitro and compared with an experimental oxime (kamiloxime; K-27) and pralidoxime. In silico the molecular interactions between AChE and oximes were examined and binding energies were assessed. LogP (predicted log of the octanol/water partition coefficient) was estimated. In vitro the intrinsic ability of the oximes to inhibit AChE (IC50) and their reactivation potency (R50) when used in paraoxon inhibited human RBC-AChE was determined. Molecular docking revealed that K378 and K727 bind to the peripheral site(s) with high binding energies in contrast to the central binding of K-27 and pralidoxime. LogP values indicating that the novel compounds are significantly less hydrophilic than K-27 or pralidoxime. IC50 of K378 and K727 were comparable (0.9 and 1?µM, respectively) but orders of magnitude lower than comparators. R50 values revealed their inability to reactivate paraoxon inhibited AChE. It is concluded that the novel oximes K378 and K727 are unlikely to be clinically useful. The in silico and in vitro studies described allow avoidance of unnecessary in vivo animal work and contribute to the reduction of laboratory animal use. 相似文献
7.
Vesna Jacevic Kamil Kuca Zoran Milovanovic Aleksandra Bocarov-Stancic Ilija Rancic Dubravko Bokonjic 《Toxin reviews》2018,37(2):123-127
Cytoprotector amifostine (AMI) was given in a dose of 50, 100 or 150?mg/kg ip in rats treated with several highly toxic doses of T-2 toxin. The best survival rate (24?h and 7?days after treatment) was obtained with AMI50 (50?mg/kg ip). After T-2 intoxication, a peak in the mean number of gastric lesions (petechiae and ulcerations) was reached on the third day (26.40?±?6.24). Administration of AMI50 reduced, almost completely, the total number of gastric lesions in rats acutely poisoned by 0.5 LD50 T-2 (1.5?mg/kg sc), starting with day 1 after intoxication (5.60?±?3.42). 相似文献
8.
The New Acetylcholinesterase Inhibitors PC‐37 and PC‐48 (7‐Methoxytacrine‐Donepezil‐Like Compounds): Characterization of Their Metabolites in Human Liver Microsomes,Pharmacokinetics and In Vivo Formation of the Major Metabolites in Rats 下载免费PDF全文
Jana Zdarova Karasova Martin Mzik Milos Hroch Jan Korabecny Eugenie Nepovimova Viktor Vorisek Vladimir Palicka Kamil Kuca 《Basic & clinical pharmacology & toxicology》2018,122(4):373-382
The objective of this study was to elucidate the pharmacokinetics and metabolite formation of newly developed non‐selective AChE/BChE 7‐MEOTA‐donepezil‐like inhibitors for potential therapeutic use in Alzheimer's disease (AD) patients. The chemical structures of metabolites were defined during incubation with human liver microsomes, and subsequently, the metabolization was verified in in vivo study. In vitro metabolic profiling revealed the formation of nine major metabolites in the case of PC‐37 and eight metabolites of PC‐48. Hydroxylation and the enzymatic hydrolysis of bonds close to the piperazine ring appeared to be the principal metabolic pathways in vitro. Of these metabolites, M1–M7 of PC‐37 and M1–M6 of PC‐48 were confirmed under in vivo conditions. Pilot pharmacokinetic experiments in rats were focused on the absorption, distribution and elimination of these compounds. Absorption after i.m. application was relatively fast; the bioavailability expressed as AUCtotal was 28179 ± 4691 min.ng/mL for PC‐37 and 23374 ± 4045 min.ng/mL for PC‐48. Both compounds showed ability to target the central nervous system, with brain concentrations exceeding those in plasma. The maximal brain concentrations are approximately two times higher than the plasma concentrations. The relatively high brain concentrations persisted throughout the experiment until 24 hr after application. Elimination via the kidneys (urine) significantly exceeded elimination via the liver (bile). All these characteristics are crucial for new candidates intended for AD treatment. The principle metabolic pathways that were verified in the in vivo study do not show any evidence for formation of extremely toxic metabolites, but this needs to be confirmed by further studies. 相似文献
9.
10.
Kamil W Al Habashneh R Khader Y Al Bayati L Taani D 《Journal of periodontal research》2011,46(5):616-621
Kamil W, Al Habashneh R, Khader Y, Al Bayati L, Taani D. Effects of nonsurgical periodontal therapy on C‐reactive protein and serum lipids in Jordanian adults with advanced periodontitis. J Periodont Res 2011; 46: 616–621. © 2011 John Wiley & Sons A/S Background and Objective: Data on whether periodontal therapy affects serum CRP levels are inconclusive. The aim of this study was to determine if nonsurgical periodontal therapy has any effect on CRP and serum lipid levels in patients with advanced periodontitis. Material and Methods: Thirty‐six systemically healthy patients, ≥ 40 years of age and with advanced periodontitis, were recruited for the study. Patients were randomized consecutively to one of two groups: the treatment group (n = 18) or the control group (n = 18). Treated subjects received nonsurgical periodontal therapy, which included oral hygiene instructions and subgingival scaling and root planing. Systemic levels of inflammatory markers [C‐reactive protein (CRP) and the lipid profile] were measured at baseline and 3 mo after periodontal therapy. Results: Nonsurgical periodontal therapy in the treatment group resulted in a significant reduction in the serum CRP level. The average CRP level decreased from 2.3 mg/dL at baseline to 1.8 mg/dL (p < 0.005) after 3 mo of periodontal therapy. The average reduction (95% confidence interval) in CRP was 0.498 (95% confidence interval = 0.265–0.731). In the treatment group, the reduction in CRP was significantly, linearly and directly correlated with the reduction in the plaque index, the gingival index and the percentage of sites with pocket depth ≥ 7 mm (Pearson correlation coefficient = 0.746, 0.425 and 0.621, respectively). Nonsurgical periodontal therapy had no effect on the lipid parameters. Conclusion: This study demonstrated that nonsurgical periodontal therapy results in a significant reduction in the serum CRP level. The effect of this outcome on systemic disease is still unknown. 相似文献