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Bahia A. Moussa Asmaa A. El‐Zaher Mohamed K. El‐Ashrey Marwa A. Fouad 《Drug testing and analysis》2019,11(6):886-897
With the aim of studying their in vitro and in vivo pharmacokinetics, new chromatographic methods were developed for the determination of three new roflumilast synthetic analogs ( I?III ) as PDE‐4B inhibitors in rat liver S9 fraction, phosphate buffered saline, pH 7.4, and human and rat plasma. The developed high performance liquid chromatography?ultra violet (HPLC?UV) methods were performed on a Zorbax Eclipse C8 column and UV detection was carried out at 215 nm. The three compounds were tested for their metabolic stability and were found to be metabolically more stable than roflumilast especially the 2‐mercaptobenzothiazol‐6‐yl analog ( III ) which displayed an in vitro half‐life time (247.55 minutes) higher than that of roflumilast (12.29 minutes) and a low in vitro clearance of 5.67 mL/min./kg. Possible phase I metabolites were investigated using ultra‐performance liquid chromatography?tandem mass spectrometry (UPLC–MS/MS) showing hydroxylation of the unsubstituted benzothiazol‐2‐yl ( I ) and benzothiazole‐6‐yl ( II ) analogs and a cleaved benzothiazole metabolite of the 2‐mercaptobenzothiazol‐6‐yl analog ( III ). Plasma protein binding affinity was tested using equilibrium membrane dialysis method showing a very high percentage (more than 95%) of plasma protein binding of compounds I and II where compound III exhibited lower percentage (53.71%) demonstrating its accessibility for tissue distribution. Also, a UPLC–MS/MS method was developed using an Acquity UPLC BEH shield RP C18 column to be applied to an in vivo pharmacokinetic study in rats following a subcutaneous dose (1 mg/kg). Compounds I?III showed improved in vivo pharmacokinetic parameters especially compound III which displayed a half‐life 3‐fold greater than roflumilast (21 hours) and a Cmax value of 113.958 ng/mL. Accordingly, this new chemical entity should be subjected to further investigation as it can be a good drug candidate for treating chronic obstructive pulmonary disease. 相似文献
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das Neves J Pinto E Teixeira B Dias G Rocha P Cunha T Santos B Amaral MH Bahia MF 《Drugs》2008,68(13):1787-1802
Vulvovaginal candidosis is a common worldwide female medical problem, occurring mostly in women of childbearing age. Currently available options for the treatment of this condition include local and oral (systemic) therapy. Both alternatives have been considered equally effective in the treatment of uncomplicated vulvovaginal candidosis, although oral regimens are often preferred by physicians and women. However, local treatment presents several advantageous and unique features that may favour this therapeutic approach. The availability of numerous antifungal drugs and products for topical administration makes the selection quite challenging as this task is mostly based on personal experience or anecdotal data. Also, recent advances have been made in topical antifungal formulations and there is an increasing availability of over-the-counter products. Therefore, a review of both general and practical considerations related to the local treatment of vulvovaginal candidosis is timely.In summary, azoles and short-term regimens are usually recommended for the local treatment of vulvovaginal candidosis, with nystatin and boric acid considered as second-line alternatives. Unconventional approaches may also be regarded as suitable in patients refractory to usual treatments. In addition to the susceptibility of implicated Candida spp. to the antifungal agents, this choice should take into consideration other important issues such as particular situations (e.g. pregnancy, menopause, drug hypersensitivity), women's preferences, and the availability, particularities and cost of antifungal formulations. 相似文献
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Inhibitors of Microsomal Prostaglandin E2 Synthase‐1 Enzyme as Emerging Anti‐Inflammatory Candidates
Malkeet Singh Bahia Yogesh Kumar Katare Om Silakari Bhawna Vyas Pragati Silakari 《Medicinal research reviews》2014,34(4):825-855
Cyclooxygenases (COX‐1 and COX‐2) catalyze the conversion of arachidonic acid (AA) into PGH2 that is further metabolized by terminal prostaglandin (PG) synthases into biologically active PGs, for example, prostaglandin E2 (PGE2), prostacyclin I2 (PGI2), thromboxane A2 (TXA2), prostaglandin D2 (PGD2), and prostaglandin F2 alpha (PGF2α). Among them, PGE2 is a widely distributed PG in the human body, and an important mediator of inflammatory processes. The successful modulation of this PG provides a beneficial strategy for the potential anti‐inflammatory therapy. For instance, nonsteroidal anti‐inflammatory agents (NSAIDs), both classical nonselective (cNSAIDs) and the selective COX‐2 inhibitors (coxibs) attenuate the generation of PGH2 from AA that in turn reduces the synthesis of PGE2 and modifies the inflammatory conditions. However, the long‐term use of these agents causes severe side effects due to the nonselective inhibition of other PGs, such as PGI2 and TXA2, etc. Microsomal prostaglandin E2 synthase‐1 (mPGES‐1), a downstream PG synthase, specifically catalyzes the biosynthesis of COX‐2‐derived PGE2 from PGH2, and describes itself as a valuable therapeutic target for the treatment of acute and chronic inflammatory disease conditions. Therefore, the small molecule inhibitors of mPGES‐1 would serve as a beneficial anti‐inflammatory therapy, with reduced side effects that are usually associated with the nonselective inhibition of PG biosynthesis. 相似文献
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Matheus Santos Melo Luís Antônio Alvarado Cabrera Shirley Verônica Melo Almeida Lima Allan Dantas dos Santos Lilian Maria Garcia Bahia Oliveira Renata Carla de Oliveira Janaína de Sousa Menezes Josivânia Arrais de Figueiredo Viviane Fragoso de Moura Lane Francisco Edilson Ferreira de Lima Júnior Rosalynd Vinicios da Rocha Moreira 《Tropical medicine & international health : TM & IH》2023,28(6):476-485