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排序方式: 共有899条查询结果,搜索用时 31 毫秒
21.
Stephen E. Daniels Hartley C. Atkinson Ioana Stanescu Chris Frampton 《Clinical therapeutics》2018,40(10):1765-1776.e5
Purpose
Acute pain is a significant burden to the individual and to society. There is a clear need for a pain medication that provides improved analgesia over common analgesics, without compromising tolerability. The goal of this study was to determine the efficacy of a new fixed-dose combination of acetaminophen 975 mg and ibuprofen 292.5 mg (FDC 975/292.5) relative to acetaminophen or ibuprofen monotherapy, or placebo.Methods
This prospective, multicenter, randomized, double-blind, placebo-controlled, Phase III trial included 408 adult volunteers aged 18 to 60 years experiencing moderate to severe pain after surgical removal of at least 2 impacted third molars. Subjects were randomized in a 3:3:3:2 ratio to the following interventions: FDC 975/292.5, acetaminophen 975 mg, ibuprofen 292.5 mg, and placebo. Self-reported pain intensity scores were recorded over a 48-hour double-blind treatment period using a 100-mm visual analog scale. In addition, time to perceptible and meaningful pain relief was assessed by using the two-stopwatch method; use of rescue medication (oxycodone) was recorded; and patients rated their pain relief on a 5-point categorical scale. All adverse events during the 30-day study period were assessed.Findings
The majority of participants were female (67.4%) and white (90.0%), with a mean age of 24.8 years. Demographic and baseline characteristics were balanced across treatment groups, with a mean baseline pain score of 56.4 mm. The primary end point was the time-adjusted sum of pain intensity differences over 48 hours, which was found to be significantly greater for FDC 975/292.5 than for both monotherapies and placebo (all, P < 0.001). The robustness of the procedures used in the calculation of the primary end point was confirmed in a series of sensitivity analyses. Statistical superiority of the combination was evident in all secondary end points (time to meaningful pain relief, maximum pain score, response rate, participants using supplementary analgesia, time to rescue, oxycodone consumption, and categorical pain relief score) with the exception of time to perceptible pain relief versus monotherapies and the time to peak response versus ibuprofen. The percentage of patients reporting adverse events was 37.3% in the FDC 975/292.5 group, with no significant differences between treatment groups. Nausea was the most common adverse event across all groups.Implications
Overall, the fixed-dose combination of acetaminophen and ibuprofen provided greater and more rapid analgesia than comparable doses of either agent alone or placebo in adults after removal of impacted third molars. ClinicalTrials.gov identifier: NCT01420653. 相似文献22.
23.
Co‐administration of N‐Acetylcysteine and Acetaminophen Efficiently Blocks Acetaminophen Toxicity 下载免费PDF全文
Solomon E Owumi James P Andrus Leonard A Herzenberg Leonore A Herzenberg 《Drug development research》2015,76(5):251-258
Preclinical Research |
24.
Innate immune system plays a critical role in determining the progression and severity of acetaminophen hepatotoxicity 总被引:8,自引:0,他引:8
BACKGROUND & AIMS: Inflammatory mediators released by nonparenchymal inflammatory cells in the liver have been implicated in the progression of acetaminophen (APAP) hepatotoxicity. Among hepatic nonparenchymal inflammatory cells, we examined the role of the abundant natural killer (NK) cells and NK cells with T-cell receptors (NKT cells) in APAP-induced liver injury. METHODS: C57BL/6 mice were administered a toxic dose of APAP intraperitoneally to cause liver injury with or without depletion of NK and NKT cells by anti-NK1.1 monoclonal antibody (MAb). Serum alanine transaminase (ALT) levels, liver histology, hepatic leukocyte accumulation, and cytokine/chemokine expression were assessed. RESULTS: Compared with APAP-treated control mice, depletion of both NK and NKT cells by anti-NK1.1 significantly protected mice from APAP-induced liver injury, as evidenced by decreased serum ALT level, improved survival of mice, decreased hepatic necrosis, inhibition of messenger RNA (mRNA) expression for interferon-gamma (IFN-gamma), Fas ligand (FasL), and chemokines including KC (Keratinocyte-derived chemokine); MIP-1 alpha (macrophage inflammatory protein-1 alpha); MCP-1 (monocyte chemoattractant protein-1); IP-10 (interferon-inducible protein); Mig (monokine induced by IFN-gamma) and decreased neutrophil accumulation in the liver. Hepatic NK and NKT cells were identified as the major source of IFN-gamma by intracellular cytokine staining. APAP induced much less liver injury in Fas-deficient (lpr) and FasL-deficient (gld) mice compared with that in wild-type mice. CONCLUSIONS: NK and NKT cells play a critical role in the progression of APAP-induced liver injury by secreting IFN-gamma, modulating chemokine production and accumulation of neutrophils, and up-regulating FasL expression in the liver, all of which may promote the inflammatory response of liver innate immune system, thus contributing to the severity and progression of liver injury downstream of the metabolism of APAP and depletion of reduced glutathione (GSH) in hepatocytes. 相似文献
25.
目的评估替利定治疗腰椎间盘突出症合并神经根性疼痛的疗效和安全性。方法连续将94例接受髓核摘除术的腰椎间盘突出症合并神经根性疼痛患者,以1∶1随机分为替利定(T)组和氨酚羟考酮(O)组。T组患者于术前2 h及术后4、10、16 h予盐酸替利定口服溶液100 mg,po;O组患者于同一时间予氨酚羟考酮片(每片包含羟考酮5 mg+对乙酰氨基酚325 mg)1片,po。于术前和术后24 h以内评估患者疼痛视觉模拟评分(VAS),患者整体状态(PGA)评分,使用哌替啶的人数、用量以及不良反应。结果 T组患者在术后12和24 h VAS评分(2.7±1.8 vs 3.6±1.5;2.4±1.4 vs 3.1±1.5)和PGA评分(3.3±1.9 vs 4.1±1.8;2.7±1.5 vs 3.5±1.7)均显著低于O组患者(P<0.05)。同时,T组患者因出现难以忍受的疼痛而使用哌替啶进行解救的患者比例显著低于O组患者(8.5%vs 23.4%,P=0.049)。此外,2组患者出现不良反应如恶心、便秘、呕吐、嗜睡和头晕的比例之间差异均无统计学意义(P>0.05)。结论替利定治疗腰椎间盘突出症合并神经根性疼痛疗效优于氨酚羟考酮,而安全性与氨酚羟考酮相当。 相似文献
26.
27.
Petra Thulin Gunnar Nordahl Marcus Gry Getnet Yimer Eleni Aklillu Eyasu Makonnen Getachew Aderaye Lars Lindquist C. Mikael Mattsson Björn Ekblom Daniel J. Antoine B. Kevin Park Stig Linder Alison H. Harrill Paul B. Watkins Björn Glinghammar Ina Schuppe‐Koistinen 《Liver international》2014,34(3):367-378
28.
Yicong Chang Feng Wang Yang Yang Yuanyuan Zhang Ishfaq Muhammad Rui Li Changwen Li Ying Li Chenxi Shi Xin Ma Beili Hao Fangping Liu 《Journal of applied toxicology : JAT》2019,39(12):1640-1650
Acetaminophen (APAP) is an antipyretic and analgesic, which is commonly associated with drug‐induced hepatic injury. C2‐ceramide plays a key role in mediating cell life activities, and oltipraz was extensively studied as a cancer chemopreventive agent. Glutathione S‐transferase A1 (GSTA1) acts as a vital liver detoxification enzyme. Hepatocyte nuclear factor 1 (HNF‐1) regulates various cellular signaling pathways. In this study, we investigated the effects of C2‐ceramide and oltipraz on APAP‐induced hepatocyte injury and the changes of HNF‐1 and GSTA1. Results showed that C2‐ceramide (6 μmol/L) exacerbated APAP‐induced hepatocyte injury and caused a significant decrease (P < .01) in HNF‐1 and GSTA1 expressions. Meanwhile, GSTA1 content in supernatant was significantly increased (P < .01). In contrast, oltipraz (8 μmol/L) reduced the injury and significantly elevated (P < .01) HNF‐1 and GSTA1 expressions while GSTA1 content in supernatant was significantly decreased (P < .01). In conclusion, these findings revealed that C2‐ceramide inhibited HNF‐1 and GSTA1 expression and exacerbated hepatocyte injury, while oltipraz treatment results in the reduction of hepatocyte injury, and promoted HNF‐1 and GSTA1 expression. Additionally, the changes in HNF‐1 and GSTA1 were related to APAP‐induced hepatocyte injury. These results were useful to investigate the mechanism of an antipyretic and analgesic drug combination. 相似文献
29.
An overdose of acetaminophen (APAP) causes liver injury in experimental animals and humans. The activation step (formation of reactive metabolite, N-acetyl-p-benzoquinone imine by cytochrome P450 system) and the consequent downstream pathway of oxidative stress, nitrosative stress, and inflammation play an important role in APAP-induced hepatotoxicity. Formulation of APAP with an inhibitor of the activation step would be ideal to prevent accidental and intentional APAP toxicity. Dimethyl sulfoxide (DMSO) is a common colorless, inexpensive solvent, and considered safe in human. We hypothesized that a less hepatotoxic APAP if co-formulated with DMSO. To test this hypothesis, C57BL/6 mice were given toxic dose of APAP (250 mg kg−1, i.p.) mixed with different doses of DMSO (25, 50, 100, and 200 μl kg−1). Six hours after APAP treatment, blood and lives were collected for analysis. In DMSO treated groups, there was dose-dependent decrease in markers of liver injury, alanine aminotransferase, and aspartate aminotransferase. Maximum protection was obtained with 200 μl DMSO kg−1. DMSO was shown to inhibit the activation step by decreasing the rate of GSH depletion in vivo and inhibiting cytochrome P450 system in vitro. Also the levels of lipid peroxides, nitrate/nitrite, tumor necrosis factor-alpha, and interleukin 1β were decreased significantly. In conclusion, DMSO exerts its protective action by inhibiting the metabolic activation of APAP and thus alleviating the downstream, oxidative stress, nitrosative stress, and inflammation via indirect inhibition. Our findings suggest that replacing the current APAP with APAP/DMSO formulation could prevent accidental and intentional APAP toxicity. 相似文献
30.
目的建立复方对乙酰氨基酚片中阿司匹林、咖啡因和对乙酰氨基酚测定的氢核磁共振波谱方法。方法采用氘代甲醇为溶剂,马来酸为内标。采用zg30脉冲序列获取~1H-NMR谱图。测试温度:300 K;谱宽:8 012 Hz;采集时间:4.01 s:弛豫时间:20 s,样品扫描次数:64次;空扫次数:2次。并采用HPLC法测定进行比较。结果阿司匹林、对乙酰氨基酚和咖啡因平均回收率分别为101.29%、101.68%、99.13%,RSD值分别为1.15%、1.73%、1.92%。qNMR法测定结果与HPLC法测定结果基本一致。结论氢核磁共振波谱法操作简便、快速,能准确测定复方对乙酰氨基酚片中阿司匹林、咖啡因和对乙酰氨基酚。 相似文献