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991.
Tetrabenazine (TBZ) is widely used to treat hyperkinetic movement disorders in adults; however, published experience with the drug in children is limited. Common side effects of TBZ include drowsiness, sedation, weakness, Parkinsonism, depression, and acute akathisia, all of which are reversible with decreased doses. We report here a 7-year-old girl with rheumatic chorea who developed acute akinesia of all four limbs and dysarthria due to TBZ therapy. Withdrawal of the drug led to rapid improvement within 18 hours. 相似文献
992.
Piperacillin/tazobactam is a commonly prescribed antibiotic and is generally considered safe. We report a case of a 2-year-old girl who developed hypokalemic metabolic alkalosis and bradycardia after receiving intravenous piperacillin-tazobactam for bronchopneumonia. Upon withdrawal of the drug, serum potassium normalized in 2 days. Hypokalemia is a serious adverse effect of piperacillin-tazobactam and should be suspected while treating patients with this drug. Early recognition and prompt withdrawal of the drug will result in lesser morbidity. 相似文献
993.
A rapid and highly sensitive method for the determination of acamprosate (ACM), in human plasma using ESI-LC-MS/MS (electrospray ionization liquid chromatography tandem mass spectrometry) in negative ionization polarity in multiple reactions monitoring (MRM) mode was developed and validated. The procedure involves a simple protein precipitation step. Chromatographic separation was carried out on a Hypersil BDS C(18) column (150 mm × 4.6 mm, 5 μm) with an isocratic mobile phase and a total run time of 2.5 min. The standard calibration curves were linear within the range of 7.04-702.20 ng/mL for ACM (r ≥ 0.990). This study briefly describes the role of ion source design on matrix effects. ACM shows matrix effects in z-spray ionization source design, whereas it has no matrix effects in orthogonal spray ion source design. This method was successfully applied to a pharmacokinetic study after oral administration of acamprosate 333 mg tablet in Indian healthy male volunteers. 相似文献
994.
Chakravarty A Shinde V Tabernero J Cervantes A Cohen RB Dees EC Burris H Infante JR Macarulla T Elez E Andreu J Rodriguez-Braun E Rosello S von Mehren M Meropol NJ Langer CJ ONeil B Bowman D Zhang M Danaee H Faron-Yowe L Gray G Liu H Pappas J Silverman L Simpson C Stringer B Tirrell S Veiby OP Venkatakrishnan K Galvin K Manfredi M Ecsedy JA 《Cancer research》2011,71(3):675-685
The mitotic kinase Aurora A is an important therapeutic target for cancer therapy. This study evaluated new mechanism-based pharmacodynamic biomarkers in cancer patients in two phase I studies of MLN8054, a small-molecule inhibitor of Aurora A kinase. Patients with advanced solid tumors received MLN8054 orally for 7 consecutive days in escalating dose cohorts, with skin and tumor biopsies obtained before and after dosing. Skin biopsies were evaluated for increased mitotic cells within the basal epithelium. Tumor biopsies were assessed for accumulation of mitotic cells within proliferative tumor regions. Several patients in the highest dose cohorts showed marked increases in the skin mitotic index after dosing. Although some tumors exhibited increases in mitotic cells after dosing, others displayed decreases, a variable outcome consistent with dual mechanisms of mitotic arrest and mitotic slippage induced by antimitotics in tumors. To provide a clearer picture, mitotic cell chromosome alignment and spindle bipolarity, new biomarkers of Aurora A inhibition that act independently of mitotic arrest or slippage, were assessed in the tumor biopsies. Several patients, primarily in the highest dose cohorts, had marked decreases in the percentage of mitotic cells with aligned chromosomes and bipolar spindles after dosing. Evidence existed for an exposure-effect relationship for mitotic cells with defects in chromosome alignment and spindle bipolarity that indicated a biologically active dose range. Outcomes of pharmacodynamic assays from skin and tumor biopsies were concordant in several patients. Together, these new pharmacodynamic assays provide evidence for Aurora A inhibition by MLN8054 in patient skin and tumor tissues. 相似文献
995.
996.
Grobmyer SR Morse DL Fletcher B Gutwein LG Sharma P Krishna V Frost SC Moudgil BM Brown SC 《Journal of surgical oncology》2011,103(4):317-325
Approaches for breast cancer treatment are invasive, disfiguring, have significant side-effects, and are not always curative. Nanotechnology is an emerging area which is focused on engineering of materials <100 × 10(-9) m. There is significant promise for advancing nanotechnology to improve breast cancer diagnosis and treatment including non-invasive therapy, monitoring response to therapy, advanced imaging, treatment of metastatic disease, and improved nodal staging. Current approaches and important future directions are discussed. 相似文献
997.
The median survival for patients with malignant pleural mesothelioma remains extremely poor and there is a need for the development of more effective treatment modalities. The epidermal growth factor receptor is frequently over-expressed in malignant pleural mesothelioma samples and therefore may be a potential therapeutic target. Targeted EGFR therapy has been successful in non-small cell lung cancer using small molecule tyrosine kinase inhibitors and in colorectal cancer using monoclonal anti-EGFR antibodies. However, phase II clinical trials based on EGFR tyrosine kinase inhibitor therapy have so far not shown promise in mesothelioma. This review includes a background to targeted EGFR treatment strategies, explores putative therapy resistance mechanisms, including the role of predictive biomarkers, and describes the current status of targeted EGFR therapeutic strategies for mesothelioma patients. 相似文献
998.
Nandagiri VK Gentile P Chiono V Tonda-Turo C Matsiko A Ramtoola Z Montevecchi FM Ciardelli G 《Journal of the Mechanical Behavior of Biomedical Materials》2011,4(7):1318-1327
Bone regeneration can be accelerated by localized delivery of appropriate growth factors/biomolecules. Localized delivery can be achieved by a 2-level system: (i) incorporation of biomolecules within biodegradable particulate carriers (nanoparticles), and (ii) inclusion of such particulate carriers (nanoparticles) into suitable porous scaffolds. In this study, freeze-dried porous chitosan–gelatin scaffolds (CH–G: 1:2 ratio by weight) were embedded with various amounts of poly(lactide-co-glycolide) (PLGA) nanoparticles, precisely 16.6%, 33.3% and 66.6% (respect to CH–G weight). Scaffolds loaded with PLGA nanoparticles were subjected to physico-mechanical and biological characterizations including morphological analysis, swelling and dissolution tests, mechanical compression tests and cell viability tests. Results showed that incorporation of PLGA nanoparticles into porous crosslinked CH–G scaffolds: (i) changed the micro-architecture of the scaffolds in terms of mean pore diameter and pore size distribution, (ii) reduced the dissolution degree of the scaffolds, and (iii) increased the compressive modulus. On the other hand, the water uptake behavior of CH–G scaffolds containing PLGA nanoparticles significantly decreased. The incorporation of PLGA nanoparticles did not affect the biocompatibility of CH–G scaffolds. 相似文献
999.
Crison JR Timmins P Keung A Upreti VV Boulton DW Scheer BJ 《Journal of pharmaceutical sciences》2012,101(5):1773-1782
The dependency of metformin in vivo disposition on the rate and extent of dissolution was studied. The analysis includes the use of fundamental principles of drug input, permeability, and intestinal transit time within the framework of a compartmental absorption transit model to predict key pharmacokinetic (PK) parameters and then compare the results to clinical data. The simulations show that the maximum plasma concentration (Cmax) and area under the curve (AUC) are not significantly affected when 100% of drug is released within 2 h of oral dosing, which was confirmed with corresponding human PK data. Furthermore, in vitro dissolution profiles measured in aqueous buffers at pH values of 1.2, 4.5, and 6.8 were slower than in vivo release profiles generated by deconvolution of metformin products that were bioequivalent. On the basis of this work, formulations of metformin that release 100% in vitro in a time period equal to or less than two hours are indicated to be bioequivalent. The use of modeling offers a mechanistic-based approach for demonstrating acceptable bioperformance for metformin formulations without having to resort to in vivo bioequivalence studies and may be more robust than statistical comparison of in vitro release profiles. This work further provides a strategy for considering Biopharmaceutics Classification System (BCS) Class 3 compounds to be included under biowaiver guidelines as for BCS Class 1 compounds. © 2012Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:1773–1782, 2012 相似文献
1000.
Tamayo NA Bo Y Gore V Ma V Nishimura N Tang P Deng H Klionsky L Lehto SG Wang W Youngblood B Chen J Correll TL Bartberger MD Gavva NR Norman MH 《Journal of medicinal chemistry》2012,55(4):1593-1611
The transient receptor potential melastatin type 8 (TRPM8) is a nonselective cation channel primarily expressed in a subpopulation of sensory neurons that can be activated by a wide range of stimuli, including menthol, icilin, and cold temperatures (<25 °C). Antagonism of TRPM8 is currently under investigation as a new approach for the treatment of pain. As a result of our screening efforts, we identified tetrahydrothienopyridine 4 as an inhibitor of icilin-induced calcium influx in CHO cells expressing recombinant rat TRPM8. Exploration of the structure-activity relationships of 4 led to the identification of a potent and orally bioavailable TRPM8 antagonist, tetrahydroisoquinoline 87. Compound 87 demonstrated target coverage in vivo after oral administration in a rat pharmacodynamic model measuring the prevention of icilin-induced wet-dog shakes (WDS). 相似文献