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61.
Antoine Minne Hlne Boireau Maria Joao Horta Rita Vanbever 《European journal of pharmaceutics and biopharmaceutics》2008,70(3):839-844
The aim of this study was to investigate the influence of formulation excipients on physical characteristics of inhalation dry powders prepared by spray-drying. The excipients used were a series of amino acids (glycine, alanine, leucine, isoleucine), trehalose and dipalmitoylphosphatidylcholine (DPPC). The particle diameter and the powder density were assessed by laser diffraction and tap density measurements, respectively. The aerosol behaviour of the powders was studied in a Multi-Stage Liquid Impinger. The nature and the relative proportion of the excipients affected the aerosol performance of the powders, mainly by altering powder tap density and degree of particle aggregation. The alanine/trehalose/DPPC (30/10/60 w/w/w) formulation showed optimal aerodynamic behaviour with a mass median aerodynamic diameter of 4.7 μm, an emitted dose of 94% and a fine particle fraction of 54% at an airflow rate of 100 L/min using a Spinhaler inhaler device. The powder had a tap density of 0.10 g/cm3. The particles were spherical with a granular surface and had a 4 μm volume median diameter. In conclusion, optimization of the aerosolization properties of inhalation dry powders could be achieved by appropriately selecting the composition of the particles. 相似文献
62.
Morten Jonas Maltesen Simon Bjerregaard Lars Hovgaard Svend Havelund Marco van de Weert 《European journal of pharmaceutics and biopharmaceutics》2008,70(3):828-838
Quality by design (QBD) refers to a holistic approach towards drug development. Important parts of QBD include definition of final product performance and understanding of formulation and process parameters. Inhalation of proteins for systemic distribution requires specific product characteristics and a manufacturing process which produces the desired product. The objective of this study was to understand the spray drying process of insulin intended for pulmonary administration. In particular, the effects of process and formulation parameters on particle characteristics and insulin integrity were investigated. Design of experiments (DOE) and multivariate data analysis were used to identify important process parameters and correlations between particle characteristics. The independent parameters included the process parameters nozzle, feed, and drying air flow rate and drying air temperature along with the insulin concentration as a formulation parameter. The dependent variables included droplet size, geometric particle size, aerodynamic particle size, yield, density, tap density, moisture content, outlet temperature, morphology, and physical and chemical integrity. Principal component analysis was performed to find correlations between dependent and independent variables. Prediction equations were obtained for all dependent variables including both interaction and quadratic terms. Overall, the insulin concentration was found to be the most important parameter, followed by inlet drying air temperature and the nozzle gas flow rate. The insulin concentration mainly affected the particle size, yield and tap density, while the inlet drying air temperature mainly affected the moisture content. No change was observed in physical and chemical integrity of the insulin molecule. 相似文献
63.
七氟烷在婴幼儿麻醉中的临床应用 总被引:1,自引:0,他引:1
何铭 《四川省卫生管理干部学院学报》2008,27(4):263-264
目的:探讨七氟烷在婴幼儿麻醉中的临床应用。方法:选择145例3月~5岁拟在气管插管全身麻醉下行择期外科手术的患儿。以七氟烷进行麻醉诱导与维持麻醉,以BIS判定麻醉深度。记录开始吸入七氟烷至BIS降至40~50的时间;血压心率变化;患者苏醒时间;诱导期及麻醉恢复期患者的反应。结果:BIS降至40~50的时间为90.87±32.5s;血流动力学指标较稳定,无一例心率减慢、血压下降;有27例(18.6%)患儿在麻醉诱导时出现体动,无一例呛咳、屏气和喉痉挛发生;苏醒时间10.6±3.0min;5例(3.4%)出现恶心但无呕吐,有97例(66.9%)患儿在苏醒后出现躁动:送出手术室时间为19.6±5.3min。结论:七氟烷用于婴幼儿进行麻醉诱导和维持具有诱导快、苏醒快、副作用少、麻醉深度易于调控等诸多优点,可安全地用于婴幼儿临床麻醉。 相似文献
64.
65.
66.
地氟醚循环紧闭麻醉的研究 总被引:1,自引:0,他引:1
目的:研究气管插管后预氧对地氟醚循环紧闭麻醉过程中低氧的预防作用,以及维持1.0 MAC麻醉状态其挥发器刻度(Cv)的调整方法。方法:80例择期颅脑手术病人,随机分为预氧组和无预氧组。麻醉诱导前不行紧闭面罩吸氧去氮,仅在呼吸减弱、停止时给予面罩辅助、控制呼吸,气管插管后接Ohmeda麻醉呼吸机。预氧组用5L/min氧流量进行正压通气3min(预氧),然后降低氧低流量紧闭吸入地氟醚;无预氧组直接紧闭吸入地氟醚。两组均以1.0MAC维持麻醉。分别记录两组吸入氧浓度(FiO2)下降至30%的时间和再充氧后的变化情况,同时记录Cv分别维持于不同刻度的时间。结果:预氧组FiO2首次降至30%的时间[(404.8±19.5)min]明显长于无预氧组[(246.5±95.7)min],预氧组在术中各个时刻FiO2均显著高于无预氧组。维持1.0MAC麻醉时Cv置于18%、14%、12%、10%、8%、6%的时间分别为(42.6±16.5)min、(37.9±25.1)min、(47.4±32.4)min、(49.9±47.2)min、(55.2±40.2)min、(86±50.2)min。结论:地氟醚循环紧闭麻醉有发生低氧的可能,预氧可有效预防其发生;紧闭维持1.0MAC麻醉时,推荐Cv置于18%、14%、12%、10%、8%的时间分别40、40、50、50、50min。然后以6%维持。 相似文献
67.
吸入普米克令舒佐治小儿毛细支气管炎疗效观察 总被引:1,自引:0,他引:1
目的:探讨普米克令舒雾化吸入佐治小儿毛细支气管炎(毛支)的疗效。方法:将54例毛支患儿随机分为两组,两组均采用综合治疗,观察组加用普米克令舒雾化吸入,对治疗前后症状、体征持续时间、气道阻力参数进行比较。结果:观察组在治愈率、缓解喘憋、缩短哮鸣音及咳嗽持续时间、改善肺功能、降低气道阻力的作用均明显优于对照组(P<0.05)。结论:普米克令舒雾化吸入治疗小儿毛支,可缩短病程,改善肺功能,疗效确切,且方便、安全,可作为佐治毛支的主要药物。 相似文献
68.
目的 探讨博利康尼、普米克令舒、沐舒坦雾化吸入佐治毛细支气管炎的疗效。方法将54例毛细支气管炎惠儿随机分成治疗组和对照组,2组均采用综合治疗,治疗组加用博利康尼、普米克令舒、沐舒坦空气压缩泵雾化吸入治疗。对治疗后症状、体征改善时间进行比较。结果治疗组治愈率93.3%,对照组治愈率62.5%,2组疗效比较(P〈0.05~0.01),差异有统计学意义。2组症状、体征持续时间及病程上比较(P〈0.01),差异也有统计学意义。结论博利康尼、普米克令舒、沐舒坦雾化吸入能改善毛细支气管炎的治愈过程,起效快,副作用小,疗效满意。 相似文献
69.
An experimental group of 16 male pure-bred mice was exposed to perchloroethylene gas at 300ppm for 6h daily for 5 days. Histopathological study of the nasal mucosa was performed sequentially 1, 2, 4, and 7 days after exposure. Erosion of the olfactory epithelium and dilatation of Bowman's glands were observed from 1 to 7 days after exposure. Atrophy of the olfactory nerves was observed from 4 to 7 days after exposure. At 4 days after exposure, regenerating epithelial cells were observed, indicating that these cells represented the first step of the repair process after exposure. Nonetheless, epithelial degeneration in the nasal mucosa without erosion was observed for 4–7 days after exposure. Such epithelial lesions were more severe in the olfactory mucosa and appeared earlier than in other sites in the respiratory mucosa. The present study revealed that perchloroethylene gas exerted a more potent harmful action on the olfactory mucosa than on the general respiratory mucosa. 相似文献
70.
Experimental Zygomycosis Due to Rhizopus spp. Infection by Various Routes in Guinea-Pigs, Rats and Mice 总被引:2,自引:0,他引:2
Summary: Streptozotocin-diabetes was induced in Swiss mice and in Wistar rats. Hematological examination was performed before streptozotocin was administered, and for 5 weeks afterwards. Leukocytosis was present in all animals. Severe diabetes was found, and it persisted during the 13-week follow-up period. Serum glucose levels were controlled weekly. Nondiabetic animals infected by inhalation or by intranasal instillation with Rhizopus microsporus var. rhizopodiformis remained negative as well as diabetic animals infected by inhalation. In the intranasally instilled mice and rats, 33% and 67% respectively contracted severe zygomycosis. Non-compromised guinea-pigs and mice were infected intravenously or intraperitoneally with Rhizopus microsporus var. rhizopodiformis or Rh. oryzae. The guinea-pig infected with small inocula was more sensitive than the mouse, and developed fatal zygomycosis with invasion of almost all organs and production of erythematous ulcerative skin eruptions. Fatal disease was also obtained in mice infected intravenously, but not intraperitoneally. Anatomopathology of the various organs and lesions revealed profuse invasion of various organs including brain, lungs, blood vessels, etc. Large coenocytic hyphae were present. In the lungs and the spleen of the guinea-pig and in the pelvic cavity of the mouse, various forms of large vesicles and sporangium-like elements were observed. The hyphae were in general distorted, broad, irregular and rarely septated. The infection of guinea-pigs with Rhizopus spp. is proposed as a model for the study of the infection. It presents all aspects of zygomycosis that may occur in man and animals, especially in compromised or largely exposed individuals. Zusammenfassung: Streptozotocin-Diabetes wurde bei Schweizer Mäusen und Wistar-Ratten erzeugt. Hämatologische Prüfungen wurden vor und 5 Wochen nach der Streptozotocin-Verabreichung durchgeführt. Bei allen Tieren lag Leukozytose vor. Es wurde ein schwerer Diabetes erzielt, der während der 13wöchigen Beobachtungsperiode anhielt. Die Serumglucosespiegel wurden wöchentlich kontrolliert. Nichtdiabetische Tiere blieben nach Inhalation oder intranasaler Instillation von Rhizopus microsporus var. rhizopodiformis negativ genau so wie die diabetischen Tiere, die durch Inhalation infiziert wurden. Nach intranasaler Instillation zeigten 33% der Mäuse und 67% der Ratten eine schwere Zygomykose. Immunkompetente Meerschweinchen und Mäuse wurden i.v. oder i.p. mit Rhizopus microsporus var. rhizopodiformis oder Rh. oryzae infiziert. Die mit kleinen Inokula infizierten Meerschweinchen erwiesen sich als empfindlicher als die Mäuse. Sie entwickelten eine tödliche Zygomykose unter Invasion fast aller Organe und Bildung erythematöser ulzerativer Hauteruptionen. Durch i.v., nicht jedoch durch i.p. Injektion ließen sich bei Mäusen tödliche Erkrankungen erzeugen. Die Anatomopathologie ergab schwere Invasion verschiedener Organe, z. B. Gehirn, Lungen, Blutgefäße. Große coenozytische Hyphen waren anwesend. In Lungen und Milz der Meerschweinchen und im Beckenhohlraum der Mäuse wurden verschiedene Formen großer Vesikeln und schwammartiger Elemente beobachtet. Die Hyphen waren im allgemeinen verzerrt, breit, unregelmäßig und zeigten selten Trennwände. Die Infektion mit Rhizopus spp. beim Meerschweinchen wird als Modell zur Untersuchung dieser Infektionsart vorgeschlagen, da sie alle Aspekte der Zygomykose, die bei Tier und Mensch, insbesondere bei immunkompromittierten oder stark exponierten Individuen auftreten kann, zeigt. 相似文献