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31.
A coprocessing/formulation approach for increasing the solubility of poorly soluble drugs using solid dispersions is presented, whereby the active pharmaceutical ingredients (API) retains its crystalline state. The approach uses a biopolymer naturally produced as dendrimeric nanoparticles that has been surface-modified to act as a solubilizing agent. The solubilizing agent is enabled by hot melt extrusion to produce the solid dispersions. Four APIs, phenytoin (PHT), griseofulvin, ibuprofen, and loratadine were used as model compounds to evaluate solubility enhancement. The rank order in solubility enhancement follows that of the hydrophobicity of the APIs. The APIs remained predominantly crystalline after hot melt extrusion processing. However, APIs with weak crystal structure (ibuprofen and loratadine) underwent measurable crystallinity loss. The solubilizing power of the modified biopolymer increases with increasing hydrophobicity and strength of the crystal structure. The solubility is described in terms of a parallel liquid-phase partition-association. For one API (PHT), solubility enhancement was minimal. The dissimilar behavior of PHT is discussed in terms of the polarity match between the API and the hydrophobic microenvironment in the solubilizing agent. This approach is expected to apply to a large number of poorly soluble drugs, offering a complementary approach to existing processing and formulation drug solubilization methods. 相似文献
32.
目的 测定Enmein的平衡溶解度、油水分配系数,考察环糊精对其包合作用,为制剂研究奠定基础。方法 采用HPLC测定Enmein在不同溶剂中的平衡溶解度;采用摇瓶法测定Enmein在不同条件下的油水分配系数;以羟丙基-β-环糊精(HP-β-CD)、羟丙基-γ-环糊精(HP-γ-CD)2种材料制备Enmein包合物,经溶解度试验,比较溶解性能的变化。结果 (25±0.5)℃振摇24 h,Enmein在纯水中溶解度为(239.32±4.99)μg·mL-1,在多种常见的有机溶剂中微溶,在常用的药用油溶剂中不溶;正辛醇-水体系中,测得Enmein油水分配系数P为4.64,不同生理pH环境及环糊精材料,对其lgP影响不大;经过2种材料包合后,Enmein的溶解度有所提高,其中以HP-γ-CD的增溶效果最好。结论 Enmein在水、常见的药用油溶剂中溶解性均不好;消化道生理pH变化及包合材料对Enmein的吸收影响不大;用Enmein的HP-γ-CD包合物为原料制备制剂,有利于提高其生物利用度。 相似文献
33.
目的研究我国建立分级诊疗制度的困境以及相关解决政策建议。方法利用博弈论和帕累托改进理论分析促进分级诊疗制度的实施方法。结果分级诊疗的难点在于未能实现帕累托改进,即患者和政府可以在分级诊疗制度中节约成本,但医生并未得到相应的激励,因此,缺乏下沉积极性。结论若能够让政府和患者节省的一部分费用补贴给大医院医生,则这些医生就会下沉到基层医疗机构,即可以实现帕累托改进,建立分级诊疗就医秩序。 相似文献
34.
摘要:目的 探讨液体负平衡对感染性休克患者急性生理学与慢性健康状态(APACHEII)评分的影响分析。方法 选取2018年1月~2020年1月本院收治的92例感染性休克患者,按不同液体管理模式分为常规组(采用液体平衡)和研究组(采用液体负平衡管理模式)各46例。对比分析2组患者心肺功能及APACHEII评分以及不良反应。结果 管理前2组患者全心舒张末期容量指数(GED-CVI)和血管外肺水指数(EVLWI)比较无统计学差异(P>0.05),管理后2组GED-CVI、EVLWI水平均增加(P<0.05),研究组上述水平高于常规组(P<0.05);研究组和常规组均完成了管理计划,2组管理前APACHEII评分比较,差异均无统计学意义(P>0.05),管理后均低于管理前(P<0.05),管理后研究组低于常规组(P<0.05);2组患者均未见明显不良反应发生。结论 液体负平衡应用于感染性休克患者,可改善心肺功能指标,降低患者APACHEII评分,可作为临床管理及防控的参考指标。 相似文献
35.
Haiqing Xu 《Econometrics Journal》2014,17(3):241-270
In this paper, I focus on the identification and estimation of static games of incomplete information with correlated types. Instead of making the independence assumption on players' types in order to simplify the equilibrium set, I propose an approach that allows me to identify subsets of the space of covariates (i.e. publicly observed state variables in payoff functions), for which there exists a unique pure strategy Bayesian Nash equilibrium (BNE) and the equilibrium strategies are monotonic functions. Moreover, I characterize the monotonic pure strategy BNE in a simple manner and propose an estimation procedure that uses observations only from the subset of the covariate space where the game admits a unique monotonic pure strategy BNE. Furthermore, I show that the proposed estimator is ‐consistent and has a limiting normal distribution. 相似文献
36.
Hai-tao Xiao Yan Liang Cheng-yuan Lin Xia Wang Zhi-zhong Guan 《Pharmaceutical biology》2014,52(3):356-361
Context: Polygonum cuspidatum Sieb et Zucc. (Polygonaceae) possesses various pharmacological activities and has been widely using as one of the most popular and valuable Chinese herbal medicines in clinics. Its usage has increasingly attracted much of our attention and urges investigation on its bioactive components.Objective: To establish a rapid and valid approach for screening potential neuroprotective components from P. cuspidatum.Materials and methods: Potential neuroprotective components from P. cuspidatum were screened utilizing liposome equilibrium dialysis followed by high-performance liquid chromatography (HPLC) analysis. Their neuroprotective effects on modulation of protein expression of α7 nAChR, α3 nAChR and synaptophysin (SPY) on SH-SY5Y human neuroblastoma cell line (SH-SY5Y) were evaluated by means of Western blotting.Results: Two potential compounds, polydatin (C1) and emodin-8-O-β-d-glucoside (C2), were detected and identified in our study. The biological tests showed that both compounds C1 and C2, respectively, at concentrations of 0.1 and 0.25?mg/mL significantly increased protein expression of α7 and α3 nicotinic acetylcholine receptors (nAChRs) in SH-SY5Y cells. Moreover, C1 and C2 at 0.1?mg/mL significantly reversed the Aβ1-42-induced decrease of α7 and α3 nAChRs protein expression in SH-SY5Y cells. In addition, C2 at 0.1?mg/mL significantly increased protein expression of SPY in SH-SY5Y cells and Aβ1-42-induced SH-SY5Y cells whereas C1 did not provide any positive effects.Discussion and conclusion: In conclusion, our approach utilizing liposome equilibrium dialysis combined with HPLC analysis and cell-based assays is a prompt and useful method for screening neuroprotective agents. 相似文献
37.
目的建立测定具栖冬青苷、毛冬青酸血药质量浓度的方法,并测定其大鼠体外血浆蛋白结合率。方法采用高效液相色谱法和平衡透析法测定具栖冬青苷、毛冬青酸在大鼠体外血浆中的血浆蛋白结合率。结果低、中、高3种质量浓度,具栖冬青苷在大鼠体外血浆中的蛋白结合率分别为39.72%±2.68%,52.05%±3.35%和52.32%±0.76%;毛冬青酸在大鼠体外血浆中的蛋白结合率分别为55.18%±3.66%,60.79%±2.20%和47.00%±1.59%。结论建立HPLC法对具栖冬青苷和毛冬青酸进行分离,方法简便。体外实验,具栖冬青苷和毛冬青酸与大鼠血浆属中等结合型药物,且蛋白结合率与药物质量浓度无关。 相似文献
38.
Hirofumi Sakanakura Kenichi Ito Jiajie Tang Mikako Nakagawa Hiroyuki Ishimori 《Materials》2021,14(10)
Adsorption parameters such as the distribution coefficient are required to predict the release behavior of contaminants using advection-dispersion models. However, for potentially contaminant-releasing materials (PCMs) such as dredged sludge and coal ash, these parameters cannot be obtained by conventional adsorption tests. This study developed a method to determine adsorption parameters for PCMs from a set of batch tests conducted in parallel as a function of the liquid-solid ratio (LS-parallel test). This LS-parallel test was performed on sandy soil derived from marine sediment using liquid-solid ratios from 1 to 300 L/kg. The water-contact time was also changed from 10 min to 28 d to elucidate the kinetics or equilibrium of contaminants released from the sample. Adsorption parameters were successfully obtained if the substance was under adsorption control. A column percolation test was performed to confirm the effectiveness of the obtained parameters. Good agreements were observed for SO42− and B, but discrepancies remained for other substances such as F− and As suggesting that improvements are necessary in both the LS-parallel test procedure and the advection-dispersion model. 相似文献
39.
Yi-Chen Chen Jane R. Kenny Matthew Wright Cornelis E.C.A. Hop Zhengyin Yan 《Journal of pharmaceutical sciences》2019,108(3):1296-1302
Equilibrium dialysis has been widely used for the measurement of the fraction of unbound drug (fu) in plasma, but it suffers from the accuracy and reliability for low fu values. To address this concern, an orthogonal approach, called the bidirectional equilibrium dialysis, is described to simultaneously measure a pair of fu values for each drug based on equilibration in 2 opposite dialysis directions: from plasma to buffer (fu,p/b) and from buffer to plasma (fu,b/p). Hypothetically, if true equilibrium is attained in both dialysis directions, the measured fu,b/p and fu,p/b values for a given drug should converge, and thus, the ratio of fu,b/p to fu,p/b becomes unity (1.0). Thus, the ratio can be used as a tangible readout for data reliability. This methodology has been extensively tested in the present study using various drugs with distinct plasma binding characteristics. Our results clearly showed that low fu values (<0.01) could be reliably determined and verified using either the standard or dilution bidirectional equilibrium dialysis method for some known highly bound drugs; for extensively bound drugs with high logD7.4, such as montelukast, bedaquiline, and venetoclax, only a range of fu can be reported with confidence because of uncertainty in the true equilibrium. 相似文献
40.