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Meloxicam (Mel) is a non-steroidal potent anti-inflammatory drug with effective analgesic effect for various situations; e.g. postoperative pain. The early systemic exposure to Mel and hence the rapid onset of pharmacological action is limited by its poor water solubility; a situation which may be more pronounced during acute pain episode because of reduced gastric motility that affects disintegration and dissolution of solid dosage forms. To overcome delayed absorption of Mel, improvement in the dissolution behavior of Mel is essential. Firstly, Mel spherical crystalline agglomerates (SCA) were prepared. Secondly, selected Mel SCA were integrated into intraoral fast disintegrating (OF) and edible (EF) films, they possess larger surface area that leads to rapid disintegration and release of the drug into the oral cavity within seconds and hence a rapid onset of action could be achieved. Stability study of formulations resulting in faster and higher extent of dissolution and suitable mechanical properties (G3 and G12) revealed their physical and chemical stability after three months of storage under different conditions. Both G3 and G12 successfully offered rapid absorption rate and accordingly an earlier systemic exposure to Mel compared to Mobic tablets as revealed by significantly earlier T max and higher AUC0–0.5h and AUC0–4h. T max following G3 fast disintegrating film administration was comparable to that reported following Mel parenteral administration but avoiding patient inconvenience. Both films may be suitable alternative to conventional oral and intramuscular Mel especially when earlier onset of action is required (in acute conditions). 相似文献
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Letter: concordance of SVR4 and SVR12 following direct‐acting anti‐viral treatment in Egypt 下载免费PDF全文
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Nersi Jafary Omid Nika Bahari Javan Ahmad-Reza Dehpour Alireza Partoazar Morteza Rafiee Tehrani Farid Dorkoosh 《International journal of pharmaceutics》2018,535(1-2):293-307
Purpose
The aim of this research work was to explore the possibility of providing multifunctional oral insulin delivery system by conjugating several types of dipeptides on chitosan and trimethyl chitosan to be used as drug carriers.Method
Conjugates of Glycyl-glycine and alanyl-alanine of chitosan and trimethyl chitosan (on primary alcohol group of polymer located on carbon 6) were synthesized and nanoparticles containing insulin were prepared for oral delivery. Preparation conditions of nanoparticles were optimized and their performance to enhance the permeability of insulin as well as cytotoxicity of nanoparticles in Caco-2 cell line was evaluated. To evaluate the efficacy of orally administered nanoparticles, nanoparticles with the most permeability enhancing ability were studied in male Wistar rats as animal model by measuring insulin and glucose Serum levels.Result
Structural study of all the conjugates by infrared spectroscopy and nuclear magnetic resonance confirmed the successful formation of the conjugates with the desirable substitution degree. By optimizing preparation conditions, nanoparticles with expected size (157.3–197.7?nm), Zeta potential (24.35–34.37?mV), polydispersity index (0.365–0.512), entrapment efficiency (70.60–86.52%) and loading capacity (30.92–56.81%), proper morphology and desirable release pattern were obtained. Glycyl-glycine and alanyl-alanine conjugate nanoparticles of trimethyl chitosan showed 2.5–3.3 folds more effective insulin permeability in Caco-2 cell line than their chitosan counterparts. In animal model, oral administration of glycyl-glycine and alanyl-alanine conjugate nanoparticles of trimethyl chitosan demonstrated reasonable increase in Serum insulin level with relative bioavailability of 17.19% and 15.46% for glycyl-glycine and alanyl-alanine conjugate nanoparticles, respectively, and reduction in Serum glucose level compared with trimethyl chitosan nanoparticles (p?<?0.05).Conclusion
It seems that glycyl-glycine and alanyl-alanine conjugate nanoparticles of trimethyl chitosan have met the aim of this research work and have been able to orally deliver insulin with more than one mechanism in animal model. Hence, they are promising candidates for further research studies. 相似文献6.
James Kerns Hristo Piponov Cory Helder Farid Amirouche Giovanni Solitro Mark Gonzalez 《Anatomical record (Hoboken, N.J. : 2007)》2019,302(11):2030-2039
Despite the extensive literature regarding peripheral nerve stretch injuries, there are few studies that compare the nerve histology with the mechanical properties in humans. There is clinical evidence suggesting that the peroneal nerve is at greater risk for injury compared to the tibial nerve following total hip arthroplasty and hip trauma. We examined the two nerves from fresh human cadavers with or without controlled stretch. The mechanical properties, stiffness, and strain were compared with light microscopic preparations in longitudinal sections stained by the trichrome method for collagen and showing the effects of structural deformation. The tibial nerve had an average failure load 1.7× that for the peroneal nerve (P = 0.0001). Although the corresponding average stiffness showed a trend toward being larger (4.39 vs. 3.81 N/mm), the difference was not significant (P = 0.126). Histologically, the perineurium along with the underlying nerve fascicle was undulated in the control specimens and straightened out in the stretched specimens. Peroneal nerves went on to failure at lower loads and exhibited a wavy pattern on pathologic slides after failure, which shows that peroneal nerves fail mechanically before they can unfold. The tibial nerve has a biomechanical and histological advantage compared to the peroneal nerve during tensile testing, which could be the reason why it is less commonly damaged. We conclude that the perineurium is especially protective against deformation changes in human nerves relative to the respective nerve size and number of fascicles. Anat Rec, 302:2030–2039, 2019. © 2019 American Association for Anatomy 相似文献
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Objective
The purpose of this study was to characterize the effects of either acidic or combined alkaline/heat treatments on the surface of grit-blasted commercially pure (cp) titanium. The effects of the previous treatments on the shear bond strength (SBS) of cp titanium to conventional glass ionomer, resin-reinforced glass ionomer and self-adhesive resin luting cements were evaluated.Methods
Titanium discs were machined and received one of the following treatments; grit-blasting (GB), grit-blasting followed either by etching in HNO3/HF solution (GB/Ac) or by combined 5 M NaOH treatment/heat treatment at 600 °C for 1 h, then immersed for 24 h in SBF solution before cementation (GB/Ak). The treated surfaces were characterized by atomic force microscope (AFM), scanning electron microscope (SEM) and laser-induced brake-down spectroscopy (LIBS). Discs were cemented either by Fuji I, Fuji Plus or Rely X™ Unicem luting cements. The SBS was evaluated and the debonded discs were investigated by SEM.Results
Two prominent results were revealed; first, GB/Ak treatment showed the highest SBS than the other treatments (P < 0.0001). Second, Rely X™ Unicem showed the highest SBS than the other cements (P < 0.0001). Fuji I and Fuji Plus showed predominant cohesive type of failure, whereas Rely X™ showed predominant adhesive type of failure.Significance
Combined alkaline/heat treatments of commercially pure titanium surface shows to be of beneficial effect in enhancing SBS to glass ionomer, resin-modified glass ionomer and adhesive resin luting cements. 相似文献8.
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