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111.
目的研究伊曲康唑自乳化给药系统(ITZ-SEDDS)的处方工艺。方法通过溶解度实验?处方配伍和伪三相图的绘制,以自乳化时间?色泽和粒径的大小为指标,筛选油相、表面活性剂、助表面活性剂的最佳搭配和处方配比。并对ITZ-SEDDS的理化性质和体外溶出度进行了测定。结果伊曲康唑自乳化最终优化处方为:Maisine 35-1-Cremophor EL-Transcutol P=25∶30∶45。ITZ-SEDDS的粒径为162.5 nm,自乳化时间<1 min,ITZ-SEDDS在人工肠液中2 h累积溶出百分率为90.9%,是原药(0.52%)的174.8倍,市售胶囊(10.1%)的9.0倍。结论所制备的ITZ-SEDDS达到了设计要求,为ITZ的新制剂开发提供了实验依据。 相似文献
112.
Pharmacokinetics and pharmacodynamics of midazolam administered as a concentrated intranasal spray. A study in healthy volunteers 总被引:7,自引:0,他引:7
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Knoester PD Jonker DM Van Der Hoeven RT Vermeij TA Edelbroek PM Brekelmans GJ de Haan GJ 《British journal of clinical pharmacology》2002,53(5):501-507
AIMS: To investigate the pharmacokinetic and pharmacodynamic profile of midazolam administered as a concentrated intranasal spray, compared with intravenous midazolam, in healthy adult subjects. METHODS: Subjects were administered single doses of 5 mg midazolam intranasally and intravenously in a cross-over design with washout period of 1 week. The total plasma concentrations of midazolam and the metabolite 1-hydroxymidazolam after both intranasal and intravenous administration were described with a single pharmacokinetic model. beta-band EEG activity was recorded and related to midazolam plasma concentrations using an exponential pharmacokinetic/pharmacodynamic model. RESULTS: Administration of the intranasal spray led to some degree of temporary irritation in all six subjects, who nevertheless found intranasal administration acceptable and not painful. The mean (+/-s.d.) peak plasma concentration of midazolam of 71 (+/-25 ng ml-1) was reached after 14 (+/-5 min). Mean bioavailability following intranasal administration was 0.83+/-0.19. After intravenous and intranasal administration, the pharmacokinetic estimates of midazolam were: mean volume of distribution at steady state 1.11+/-0.25 l kg-1, mean systemic clearance 16.1+/-4.1 ml min-1 kg-1 and harmonic mean initial and terminal half lives 8.4+/-2.4 and 79+/-30 min, respectively. Formation of the 1-hydroxymetabolite after intranasal administration did not exceed that after intravenous administration. CONCLUSIONS: In this study in healthy volunteers a concentrated midazolam nasal spray was easily administered and well tolerated. No serious complications of the mode of administration or the drug itself were reported. Rapid uptake and high bioavailability were demonstrated. The potential of midazolam given via a nasal spray in the acute treatment of status epilepticus and other seizure disruptions should be evaluated. 相似文献
113.
胰激肽原酶油相制剂的制备及稳定性研究 总被引:1,自引:0,他引:1
目的:制备胰激肽原酶油相制剂并对其稳定性进行考察。方法:采用无水反胶束法制备胰激肽原酶油溶液,以紫外分光光度法测定胰激肽原酶的效价,测定了油溶液含药量,并考察了胰激肽原酶油相制剂的稳定性。结果:胰激肽原酶在2~10 IU·mL-1线性关系良好,回收率在98.0%~104.0%。所得胰液肽原酶油相制剂在常温下较稳定,其效价为(116.64±8.58)IU·mL-1。结论:该制剂制备简单,性质稳定。 相似文献
114.
目的研究微乳的处方因素对伊维菌素体外透皮性能的影响。方法采用改进的Franz扩散池作为离体皮肤的渗透实验装置,以紫外分光光度法测定皮肤接收液中药物浓度。以单位面积的累计渗透量(Q)和渗透系数(Js)为指标,考察了微乳处方的油相比例、混合表面活性剂质量分数和载药量对离体鼠皮透皮吸收的影响,比较了处方中加入促渗剂前后微乳释放液的渗透行为,并考察不同载体(O/W型微乳、W/O型微乳、胶束和三相溶剂系统)的体外透皮性能。结果处方中油酸最佳比例为16.1%,当其用量超过该值时,渗透效果反而下降;混合表面活性剂的质量分数为38.81%,12 h的累积渗透量达到最大值;体系载药量为2%时,渗透速率为92.97μg·cm-2·h-1,之后随载药量的增大,渗透速率显著下降;促渗剂的加入对透皮微乳的渗透速率和累计渗透量无显著改善作用,但可一定程度地减小时滞;O/W型微乳剂型的体外渗透性能最佳。结论微乳制剂作为透皮制剂载体较胶束溶液、三相溶剂系统优越,其可能是提高的浓度渗透梯度和油酸导致的角质层屏障功能降低而促进药物皮肤透过量。 相似文献
115.
116.
Purpose. Small solutes which are deposited in the alveoli by aerosolinhalation will be absorbed across the alveolo-capillary barrier.Inhalation of dioctyl sodium sulfosuccinate (DOSS) enhances absorptionwhile having little or no effect on lung function, suggesting that surfaceactive agents may be used as enhancers of alveolar absorption ofinhaled pharmaceuticals. The purpose of this study was to examinethe effects of a selection of different surface active agents onalveolar absorption.
Methods. The absorption of 99mTc-diethylene triamine pentaacetate(99mTc-DTPA) from the lungs was studied in rabbits. We studied fivedifferent surface active agents: DOSS, sodium glycodioxycholate(GDCA), sodium lauryl sulphate (NaLS), lysophosphatidyl choline(LPC) and polyoxyethylene-23-laurylether (P23LE).
Results. DOSS and GDCA both dramatically enhanced the absorptionof 99mTc-DTPA. There was a moderate effect of NaLS, no significanteffect of LPC and P23LE reduced the rate of absorption. None of thecompounds affected gas exchange or lung compliance.
Conclusions. There is a wide spectrum of effects of inhaled surfaceactive agents on the alveolar absorption of 99mTc-DTPA. Ioniccompounds such as DOSS and GDCA have the greatest effect, and furtherstudies of these classes of surface active agents for use as enhancersof alveolar absorption of pharmaceuticals seem warranted. 相似文献
117.
Cullen E Liao J Lukacsko P Niecestro R Friedhoff L 《Biopharmaceutics & drug disposition》2004,25(6):261-263
The pharmacokinetics and dose-exposure relationship of an extended-release formulation of metformin (ER-metformin) was investigated in a randomized, single-dose, four-period crossover study in 24 healthy male volunteers. During each study period, subjects received a randomly assigned dose containing 1000, 1500, 2000 or 2500 mg metformin. Blood samples were drawn 0-72 h after dosing for pharmacokinetic and dose-proportionality assessment. Although several pairwise comparisons between dose groups were significant (p<0.05) with respect to dose-normalized C(max), AUC(0-72 h), and AUC( infinity ), the magnitude of the difference across the dose range was <20% for AUC(0-72 h) and AUC( infinity ), and was < or = 30% for C(max). The results indicate a consistent and predictable increase in metformin exposure with an extended-release formulation of metformin over 1000 to 2500 mg. 相似文献
118.
Design of freeze-drying processes is often approached with a "trial and error" experimental plan or, worse yet, the protocol used in the first laboratory run is adopted without further attempts at optimization. Consequently, commercial freeze-drying processes are often neither robust nor efficient. It is our thesis that design of an "optimized" freeze-drying process is not particularly difficult for most products, as long as some simple rules based on well-accepted scientific principles are followed. It is the purpose of this review to discuss the scientific foundations of the freeze-drying process design and then to consolidate these principles into a set of guidelines for rational process design and optimization. General advice is given concerning common stability issues with proteins, but unusual and difficult stability issues are beyond the scope of this review. Control of ice nucleation and crystallization during the freezing step is discussed, and the impact of freezing on the rest of the process and final product quality is reviewed. Representative freezing protocols are presented. The significance of the collapse temperature and the thermal transition, denoted Tg', are discussed, and procedures for the selection of the "target product temperature" for primary drying are presented. Furthermore, guidelines are given for selection of the optimal shelf temperature and chamber pressure settings required to achieve the target product temperature without thermal and/or mass transfer overload of the freeze dryer. Finally, guidelines and "rules" for optimization of secondary drying and representative secondary drying protocols are presented. 相似文献
119.
Dubois EF Wagemans MF Verdouw BC Zwinderman AH Van Boxtel CJ Dekhuijzen PN Schweitzer DH 《Clinical rheumatology》2003,22(1):12-17
The medical use of glucocorticoids (GCs) is related to low bone mineral density (BMD). In this study we tested the hypothesis
that the cumulative dose of GC is not related to BMD outcome. The study was cross-sectional in design and included healthy
individuals with chronic low back pain resistant to conventional treatments. In two steroid-naive subjects cortisol and methylprednisolone
(MP) concentrations were serially assessed after a single MP depot injection (160 mg epidurally). Furthermore, in 14 men and
14 postmenopausal women, previously treated with multiple epidural MP depots, endocrine parameters were analysed in relation
to BMD outcomes. The minimal cumulative MP dose received by all 28 subjects was 3 g. In the two steroid-naive subjects, cortisol
concentrations were completely suppressed for at least 6 days and partly recovered over the course of 30 days. During this
period, MP concentrations remained detectable in plasma. In the 28 subjects, the cumulative MP dose received was 7.76±4.23
g in the men and 8.50±3.13 g in the women (mean±1SD). None of the men had osteoporosis, but osteopenia was prevalent in 78.5%
according to WHO criteria extrapolated to men. Half of the women had osteoporosis and half of them had osteopenia. The body
mass index (BMI) and endogenous oestradiol levels of the men were not related to BMD outcomes. Univariate linear relationships
in women were found between BMI and spinal (r 0.62; P=0.02) and total hip BMD (r 0.61; P=0.03), but not femoral neck BMD. In women, relationships were also found between the total and, for protein binding-corrected
oestradiol levels, and spinal BMD (r 0.70; P=0.01 and r 0.72; P=0.01, respectively) and total hip BMD (r 0.53; P=0.08 and r 0.56; P=0.05, respectively). No significance was observed between endogenous oestradiol levels and the BMD of the femoral neck. The
administration of a single MP depot injection (160 mg) resembled a systemic low peak dose GC exposure. The administration
of multiple MP depots in men and women with chronic low back pain revealed no relationship between cumulative GC dose and
BMD. These findings support the hypothesis of a non-existent relationship between cumulative GC dose and BMD outcomes in healthy
men and women with a prior GC administration of at least 3 g.
Received: 18 February 2002 / Accepted: 14 June 2002
Acknowledgements We are indebted to Dr Oscar L.H. van Hemel for advice during the performance of the study and to Ineke Bosman for excellent
laboratory support. 相似文献
120.
Chen H Zhang Z McNulty C Olbert C Yoon HJ Lee JW Kim SC Seo MH Oh HS Lemmo AV Ellis SJ Heimlich K 《Pharmaceutical research》2003,20(8):1302-1308
Purpose. The purpose of this work was to replace Cremophor-EL in the commercial paclitaxel intravenous formulation, Taxol®, using a novel high-throughput combinatorial formulation approach.
Methods. Full factorial combinations of 12 generally regarded as safe excipients at three different concentrations were screened using an automated liquid dispenser. The hit formulations were further optimized to give the final optimized formulation TPI-1. TPI-1 was then tested in rats to compare its pharmacokinetic profile to Taxol®.
Results. Of the 9,880 combinations tested in the initial screen, 19 were identified as hit combinations. These were further optimized to give the final formulation TPI-1. When tested in rats, TPI-1 was well tolerated at both the low and high doses of 5 mg/kg and 10 mg/kg, whereas Taxol® killed all the rats at the high dose. TPI-1 experienced slower elimination compared to Taxol®. Similar to Taxol®, TPI-1 also exhibited nonlinear pharmacokinetics.
Conclusions. This study demonstrated the power of a high-throughput combinatorial approach for alternative paclitaxel formulations. We believe that this approach can be applied to drug formulation in general and it can improve the speed and efficiency of drug formulation design. 相似文献