全文获取类型
收费全文 | 577篇 |
免费 | 37篇 |
国内免费 | 22篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 37篇 |
妇产科学 | 3篇 |
基础医学 | 32篇 |
口腔科学 | 26篇 |
临床医学 | 47篇 |
内科学 | 71篇 |
皮肤病学 | 10篇 |
神经病学 | 23篇 |
特种医学 | 122篇 |
外科学 | 58篇 |
综合类 | 31篇 |
预防医学 | 36篇 |
眼科学 | 31篇 |
药学 | 75篇 |
肿瘤学 | 33篇 |
出版年
2023年 | 5篇 |
2021年 | 3篇 |
2020年 | 6篇 |
2019年 | 11篇 |
2018年 | 12篇 |
2017年 | 2篇 |
2016年 | 5篇 |
2015年 | 9篇 |
2014年 | 9篇 |
2013年 | 13篇 |
2012年 | 10篇 |
2011年 | 14篇 |
2010年 | 11篇 |
2009年 | 14篇 |
2008年 | 21篇 |
2007年 | 37篇 |
2006年 | 38篇 |
2005年 | 14篇 |
2004年 | 13篇 |
2003年 | 5篇 |
2002年 | 11篇 |
2001年 | 21篇 |
2000年 | 15篇 |
1999年 | 18篇 |
1998年 | 36篇 |
1997年 | 21篇 |
1996年 | 27篇 |
1995年 | 28篇 |
1994年 | 21篇 |
1993年 | 26篇 |
1992年 | 12篇 |
1991年 | 9篇 |
1990年 | 15篇 |
1989年 | 6篇 |
1988年 | 11篇 |
1987年 | 9篇 |
1986年 | 20篇 |
1985年 | 14篇 |
1984年 | 10篇 |
1983年 | 7篇 |
1982年 | 8篇 |
1981年 | 7篇 |
1980年 | 15篇 |
1979年 | 3篇 |
1978年 | 4篇 |
1977年 | 4篇 |
1976年 | 4篇 |
1975年 | 1篇 |
1955年 | 1篇 |
排序方式: 共有636条查询结果,搜索用时 250 毫秒
101.
102.
Synthesis and biological activity of 5-thiobredinin and certain related 5-substituted imidazole-4-carboxamide ribonucleosides 总被引:1,自引:0,他引:1
S G Wood K G Upadhya N K Dalley P A McKernan P G Canonico R K Robins G R Revankar 《Journal of medicinal chemistry》1985,28(9):1198-1203
A number of 5-substituted imidazole-4-carboxamide ribonucleosides were prepared and tested for their biological activity. Treatment of 5-chloro-1-beta-D-ribofuranosylimidazole-4-carboxamide (2) with methanethiol provided 5-(methylthio)-1-beta-D-ribofuranosylimidazole-4-carboxamide (3a). Similar treatment of 2 with ethanethiol or benzenemethanethiol gave the corresponding 5-ethylthio and 5-benzylthio derivatives 3b and 3c. Oxidation of 3a and 3b with m-chloroperoxybenzoic acid furnished the corresponding sulfonyl derivatives 4a and 4b. Reductive cleavage of 3c with sodium naphthalene or Na/NH3 gave 5-mercapto-1-beta-D-ribofuranosylimidazole-4-carboxamide (5-thiobredinin, 5). Direct treatment of 2 with sodium hydrosulfide provided an alternate route to 5, the structure of which was established by single-crystal X-ray analysis. 5-Thiobredinin has a zwitterionic structure similar to that of bredinin. Glycosylation of persilylated ethyl 5(4)-methylimidazole-4(5)-carboxylate (6) with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose in the presence of SnCl4 provided a quantitative yield of the corresponding tri-O-benzoyl nucleoside 7. Debenzoylation of 7 with MeOH/NH3 at ambient temperature gave ethyl 5-methyl-1-beta-D-ribofuranosylimidazole-4-carboxylate (8). Further ammonolysis of 8 or 7 at elevated temperature and pressure gave 5-methyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (9). All of these ribonucleosides were tested in Vero cell cultures and in mice against certain viruses. Compounds 3a and 3c exhibited significant activity against vaccinia virus in vitro, whereas 4a was effective against Rift Valley fever virus in mice. 5-Thiobredinin failed to exhibit appreciable antiviral or cytostatic activity (against L1210 and P388) in cell culture. 相似文献
103.
Low-grade peripheral inflammation is often present in psychotic patients. Toll-like receptors (TLRs) are pattern-recognition molecules that initiate inflammation. Our objective was to investigate the peripheral TLR activity in psychosis. Forty schizophrenia patients, twenty bipolar patients and forty healthy controls (HC) were recruited. Donated whole blood was cultured with TLR agonists for 24 h. Cell supernatants were analysed using a multiplex enzyme-linked immunosorbent assay approach to measure IL-1β, IL-6, IL-8 and tumour necrosis factor-α (TNFα). Plasma was analysed for cytokines, cortisol and acute phase proteins. Here, we show that selective TLR agonist-induced cytokine (IL-1β, IL-6, IL-8 and TNFα) release is enhanced in stimulated whole blood from schizophrenia and bipolar patients compared with HC. An exaggerated release of IL-1β, IL-6 and TNFα following treatment with the TLR2 agonist HKLM was detected in both disorders compared with controls. Enhanced TLR4-induced increases in IL-1β for both disorders coupled with TNFα increases for bipolar patients were observed. TLR8-induced increases in IL-1β for both disorders as well as IL-6 and TNFα increases for bipolar patients were detected. TLR9-induced increases in IL-8 for schizophrenia patients were also observed. No differences in TLR1, TLR3, TLR5, TLR6 or TLR7 activity were detected. Plasma levels of IL-6 were significantly elevated in bipolar patients while TNFα levels were significantly elevated in schizophrenia patients compared with controls. Plasma acute phase proteins were significantly elevated in bipolar patients. These data demonstrate that specific alterations in TLR agonist-mediated cytokine release contribute to the evidence of immune dysfunction in psychotic disorders. 相似文献
104.
Atack JR Wafford KA Tye SJ Cook SM Sohal B Pike A Sur C Melillo D Bristow L Bromidge F Ragan I Kerby J Street L Carling R Castro JL Whiting P Dawson GR McKernan RM 《The Journal of pharmacology and experimental therapeutics》2006,316(1):410-422
7-(1,1-Dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine (TPA023) is a triazolopyridazine that binds with equivalent high (subnanomolar) affinity to the benzodiazepine binding site of recombinant human GABA(A) receptors containing an alpha1, alpha2, alpha3, or alpha5 subunit but has partial agonist efficacy at the alpha2 and alpha3 subtypes and essentially antagonist efficacy at the alpha1 and alpha5 subtypes. In rats, TPA023 gave time- and dose-dependent occupancy after oral dosing, with 50% occupancy corresponding to a dose of 0.42 mg/kg. It has anxiolytic-like activity in unconditioned (elevated plus maze) and conditioned (fear-potentiated startle and conditioned suppression of drinking) rat models of anxiety with minimum effective doses (MED; 1-3 mg/kg) corresponding to 70 to 88% occupancy. However, there was no appreciable sedation in a response sensitivity (chain-pulling) assay at a dose of 30 mg/kg, resulting in 99% occupancy. Similarly, TPA023 was robustly anxiolytic in the squirrel monkey conditioned emotional response assay, with a MED of 0.3 mg/kg, but did not produce any sedation in a lever-pressing test of sedation even at 10 mg/kg. TPA023 produced no impairment in performance in the mouse Rotarod assay, and there was only a mild interaction with ethanol. In addition to anxiolytic-like efficacy, TPA023 had anticonvulsant activity in a mouse pentylenetetrazole seizure model. Finally, TPA023 did not cause precipitated withdrawal in mice treated for 7 days with the nonselective agonist triazolam, nor did N-methyl-beta-carboline-3-carboxamide (FG 7142) precipitate withdrawal in mice treated for 7 days with TPA023. In summary, the novel alpha2/alpha3-selective efficacy profile of TPA023 translates into a nonsedating anxiolytic profile that is distinct from nonselective agonists. 相似文献
105.
Background:
Patellar dislocations are either due to superolateral contracture of the soft tissue or imbalance of the power between the vastus medialis (VM) and the vastus lateralis (VL). The imbalance of muscle power as an etiology of patellar dislocation has not been studied. Hence, we studied the recurrent, habitual and permanent dislocations of the patella with an electromyogram (EMG) of the vastus medialis, vastus lateralis, and pes anserinus, before and after realignment operations, to document the muscle imbalance and effectiveness of the realignment operation.Materials and Methods:
An electromyographic investigation was carried out on the vastus medialis and vastus lateralis in nine recurrent, 20 habitual, and 13 permanent dislocations of the patella, before and after their realignment operations. Pes anserinus transposition, which acted as a medial stabilizer of the patella, was also investigated with an EMG study, to understand its role on patellar stability at 0°, 30°, 60°, 90°, 120°, 150°, and full flexion of the knee. The age of the patients varied from nine to 30 (mean 15) years. There were 24 males and 18 females. Twenty-six patellar dislocations were on the right and 16 were on the left side.Results:
Electromyographic pictures reveal subnormal activity of the vastus medialis in all types of dislocations and similar activities of the vastus lateralis in permanent and habitual dislocations recorded pre operatively, which recovered to almost normal values postoperatively, at the mean one-year follow-up. Pes anserinus, which was used for medial stabilization of the patella after its realignment, maintained normal EMG activity before and after the operation.Conclusion:
This study is significant for understanding the imbalance of muscle activities in patients with an unstable patella, which can be rectified without recurrence after pes anserinus transposition. 相似文献106.
James?D?TuckerEmail author Karen?J?Sorensen Avima?M?Ruder Lauralynn?Taylor?McKernan Christy?L?Forrester Mary?Ann?Butler 《Environmental health : a global access science source》2011,10(1):16
Background
Significant numbers of people are exposed to tetrachloroethylene (perchloroethylene, PCE) every year, including workers in the dry cleaning industry. Adverse health effects have been associated with PCE exposure. However, investigations of possible cumulative cytogenetic damage resulting from PCE exposure are lacking. 相似文献107.
Cynthia J. Hines Thomas J. Lentz Lauralynn McKernan Pranav Rane Christine Whittaker 《Journal of occupational and environmental hygiene》2019,16(2):120-128
Bisphenol A is a commercially important chemical used to make polycarbonate plastic, epoxy resins, and other specialty products. Despite an extensive body of in vitro, animal and human observational studies on the effects of exposure to bisphenol A, no authoritative bodies in the U.S. have adopted or recommended occupational exposure limits for bisphenol A. In 2017, the National Institute for Occupational Safety and Health published a Draft process for assigning health-protective occupational exposure bands, i.e., an airborne concentration range, to chemicals lacking an occupational exposure limit. Occupational exposure banding is a systematic process that uses both quantitative and qualitative toxicity information on selected health effect endpoints to assign an occupational exposure band for a chemical. The Draft process proposes three methodological tiers of increasing complexity for assigning an occupational exposure band. We applied Tier 1 (based on the Globally Harmonized System of Classification and Labelling) and Tier 2 (based on authoritative sources/reviews) to assign an occupational exposure band to bisphenol A. Under both Tier 1 and 2, the occupational exposure band for bisphenol A was “E” (<0.01?mg/m3), an assignment based on eye damage. “E” is the lowest exposure concentration range, reserved for chemicals with high potential toxicity. If eye damage was excluded in assigning an air concentration exposure range, then bisphenol A would band as “D” (>0.01 to 0.1?mg/m3) under Tier 1 (based on reproductive toxicity and respiratory/skin sensitization) and under Tier 2 (based on specific target organ toxicity-repeated exposure). In summary, Tiers 1 and 2 gave the same occupational exposure band for bisphenol A when eye damage was included (“E”) or excluded (“D”) as an endpoint. 相似文献
108.
Mark DP Willcox 《Clinical & experimental optometry》2019,102(4):350-363
This article summarises research undertaken since 1993 in the Willcox laboratory at the University of New South Wales, Sydney on the tear film, its interactions with contact lenses, and the use of tears as a source of biomarkers for ocular and non‐ocular diseases. The proteome, lipidome and glycome of tears all contribute to important aspects of the tear film, including its structure, its ability to defend the ocular surface against microbes and to help heal ocular surface injuries. The tear film interacts with contact lenses in vivo and interactions between tears and lenses can affect the biocompatibility of lenses, and may be important in mediating discomfort responses during lens wear. Suggestions are made for follow‐up research. 相似文献
109.
110.
Frans van Workum Laura Fransen Misha DP Luyer Camiel Rosman 《World journal of gastroenterology : WJG》2018,24(44):4974-4978
Surgical innovation and pioneering are important for improving patient outcome, but can be associated with learning curves. Although learning curves in surgery are a recognized problem, the impact of surgical learning curves is increasing, due to increasing complexity of innovative surgical procedures, the rapid rate at which new interventions are implemented and a decrease in relative effectiveness of new interventions compared to old interventions. For minimally invasive esophagectomy(MIE), there is now robust evidence that implementation can lead to significant learning associated morbidity(morbidity during a learning curve, that could have been avoided if patients were operated by surgeons that have completed the learning curve). This article provides an overview of the evidence of the impact of learning curves after implementation of MIE. In addition, caveats for implementation and available evidence regarding factors that are important for safe implementation and safe pioneering of MIE are discussed. 相似文献