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941.
The aim of this study was to assess the biodistribution and pharmacokinetics of epidermal growth factor receptor (EGFR)-targeted polymer-blend nanoparticles loaded with the anticancer drugs lonidamine and paclitaxel. Plasma, tumor, and tissue distribution profiles were quantified in an orthotopic animal model of multidrug-resistant breast cancer and were compared to treatment with nontargeted nanoparticles and to treatment with drug solution. A poly(d,l-lactide-co-glycolide)-poly(ethylene glycol)-EGFR targeting peptide (PLGA-PEG-EFGR peptide) construct was synthesized for incorporation in poly(?-caprolactone) particles to achieve active EGFR targeting. An isocratic high-pressure liquid chromatography method was developed to quantify lonidamine and paclitaxel in mice plasma, tumors, and vital organs. The targeted nanoparticles demonstrated a superior pharmacokinetic profile relative to drug solution and nontargeted nanoparticles, particularly for lonidamine delivery. The first target site of accumulation was the liver, followed by the kidneys, and then the tumor mass; maximal tumor accumulation occured at 3 hours after administration. Lonidamine-paclitaxel combination therapy administered via EGFR-targeted polymer-blend nanocarriers may become a viable platform for the future treatment of multidrug-resistant cancer. FROM THE CLINICAL EDITOR: In this study the biodistribution and pharmacokinetics of epidermal growth factor receptor (EGFR)-targeted polymer-blend nanoparticles loaded with lonidamine and paclitaxel were assessed. The targeted nanoparticles demonstrated a superior pharmacokinetic profile relative to drug solution and nontargeted nanoparticles, paving the way to new therapeutic approaches for multidrug-resistant malignancies. 相似文献
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945.
Six sequential experiments were conducted on archival data of 610 U.S. Veterans seen at the Palo Alto Veteran's Affairs Hospital, to understand the dimensionalization of the Benton Visual retention test in both the recall (BVRT) and multiple-choice (BVRT-MC) format as well as the Visual Form Discrimination Test (VFDT). These tests were dimensionalized by the Wechsler Adult Intelligence Scale-Revised (WAIS-R) revealing a four-component model that explains 81.04% of the shared variance: the moderately difficult items (BVRT-MC and VFDT items 13-16) loaded with the WAIS-R Perceptual Organization, the easiest items (VFDT items 1-12, BVRT-MC items 1-12, and BVRT items 1-4) loaded separately with both WAIS-R Verbal Comprehension and Freedom from Distractibility, and the most difficult items (BVRT items 3-10) loaded weakly with WAIS-R Perceptual Organization. 相似文献
946.
Vasaghi-Gharamaleki B Keshavarz M Gharibzadeh S Sotodeh M Marvi H Mosayebnejad J Ebrahimi Takamjani I 《Acta medica Iranica》2011,49(4):225-232
The typical features of eccentric exercise-induced muscle damage is prolonged loss of muscle strength and the most rapid structural change in the fibers is loss of immunostaining for the intermediate filament protein, desmin. In this study isolated perfused rat muscle was used to examine the direct effect of temperature changes on the eccentric contraction-induced force and desmin loss. The left medial gastrocnemius muscle was separated and the entire lower limb was transferred into a prewarmed (35°C) organ bath. Temperature was adjusted to 31 or 39°C during and after eccentric contractions. Maximal isometric force and desmin loss were measured after 15 isometric or eccentric contractions. According to our data, organ bath temperature changes during or after eccentric contractions had no significant effect on force loss. However, a strong correlation between desmin loss and temperature changes during (r = 0.886, P< 0.05) and a weak correlation between desmin loss and temperature changes after (r= 0.699, P<0.05) eccentric contractions was observed. Our results suggest that cooling during eccentric contractions may decrease desmin loss but temperature changes after eccentric contractions have no effect on desmin loss. 相似文献
947.
Mohammad T.H. Nutan Sivakumar R. Vaithiyalingam Mansoor A. Khan 《Pharmaceutical development and technology》2013,18(3):307-320
The objectives of the present investigation were to prepare and characterize starch acetate (SA) with high degree of substitution (dS) and to study its prospect as film-forming agent in a controlled-release multiparticulate drug delivery system. As a part of the development process by quality by design, the objectives also included identification of critical formulation and process variables that affect the release of a drug. SA, a relatively new polymer, was characterized because it showed good film-forming properties. SA with dS 2.9 was synthesized from corn starch by paste disruption technique. It was compared with the raw material, starch, by Fourier transform infrared spectroscopy, X-ray diffraction, and molecular mass analysis. Viscosity of SA solution increased logarithmically with the polymer concentration. At higher polymer concentrations (1.5–5.0%), the solutions showed pseudoplastic behavior. Among the plasticizers tested, triacetin and triethyl citrate yielded free films with acceptable mechanical properties. The glass transition temperature (Tg) of the films could be well controlled by these plasticizers. Unplasticized film showed a Tg of 31.8°C. A trend was found that increase in triacetin concentration in SA films resulted in increase in permeability coefficient for tritiated water. Scanning electron microscopic photographs showed a clear and smooth plasticized film compared to rough unplasticized film. Dyphylline-loaded beads were coated with highly substituted SA to evaluate the main effects of the formulation and process variables on the release of the drug and to figure out the reliability of the screening design. A seven-factor, twelve-run Plackett-Burman screening design was used. The response variables were cumulative percent of drug released in 0.5, 1, 4, 8, and 12 hr. Quantitative evaluation of the design revealed that coating weight gain, plasticizer concentration, and post-drying temperature had greater influence on the drug release than the others. The main effects on drug release after 12 hr decreased in the following order: coating weight gain (?7.81), plasticizer concentration (4.96), postdrying temperature (?2.51), SA concentration (?0.80), inlet temperature (0.51), postdrying time (?0.31), and atomizing pressure (?0.28). 相似文献
948.
Farrukh Mansoor Ajmal Khan Bishnu P. Marasini Muhammad Iqbal Choudhary Muhammad Raza Shah 《Journal of Asian natural products research》2013,15(2):210-215
The bioassay-guided fractionation of Daphne retusa Hemsl. has led to the isolation of a new aryl tetrahydronaphthalene lignan derivative named as daphnretusic acid (1), along with six new source compounds such as 5,7-dihydroxyflavone (2), 7-hydroxyflavone (3), 6-methoxyflavone (4), (+) pinoresinol (5), (+) sesamin (6), and β-sitosterol-3-O-β-D-glucopyranoside (7). Their structures were elucidated by 1H NMR, 13C NMR, 1D, 2D NMR, UV, IR, and EIMS analyses. All the fractions (n-hexane, CHCl3, AcOEt, CH3OH, and water) and pure compounds (1–7) were subjected to the assay of urease and α-chymotrypsin inhibitory activities. Chloroform and methanol soluble fractions showed moderate urease inhibition. Compound 2 exhibited significant urease inhibition with IC50 value 60.4 ± 0.72 μM, whereas compounds 1 and 3–7 remained inactive during urease inhibition and α-chymotrypsin bioassays. 相似文献
949.
Rakhi B. Shah Prasanna R. Hullahalli Mobin A. Tawakkul Patrick J. Faustino Agnes Nguyenpho Mansoor A. Khan 《Clinical Research and Regulatory Affairs》2013,30(1):35-51
An isocratic reversed-phase high-performance liquid chromatographic method was developed and validated for the determination of ranitidine HCl in syrup. The samples were analyzed by high-performance liquid chromatography (HPLC). Chromatographic separation was achieved on a C18 column using an acetonitrile–aqueous phosphate buffer (20:80, v/v) elution, buffer being 10 mM disodium hydrogen phosphate brought to pH 7.1 with sodium hydroxide (0.1 N). Validation steps involved measurement of selectivity, accuracy, and precision under conditions of repeatability, reproducibility, sensitivity, and robustness. The lower limit of quantification was 10μg/mL. The validated method has been demonstrated to be reliable for the determination of ranitidine HCl and its related compound C. Stress degradation studies included exposing ranitidine HCl powder and Zantac syrup to acid, alkali, oxidation, and accelerated temperature of 50 °C for 24 hrs and photolysis for 8 hrs. The peaks of degraded products were well resolved from the drug peak. The validation of this method indicated that it could be effectively used to monitor the stability of ranitidine HCl syrup. 相似文献
950.
Denise A. Yardley Lowell Hart Linda Bosserman Mansoor N. Salleh David M. Waterhouse Maura K. Hagan Paul Richards Michelle L. DeSilvio Janine M. Mahoney Yasir Nagarwala 《Breast cancer research and treatment》2013,137(2):457-464
Lapatinib, an oral, reversible inhibitor of epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2) tyrosine kinase, has proven antitumor activity in HER2-positive metastatic breast cancer (MBC). Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is indicated for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. This was an open-label, single-arm, multicenter, Phase II study to evaluate the efficacy and safety of nab-paclitaxel plus lapatinib in women with HER2 over-expressing MBC who had received no more than one prior chemotherapeutic regimen. The primary efficacy endpoint was the overall response rate (ORR). This was defined as the percentage of patients having either a complete response (CR) or partial response (PR). Secondary efficacy endpoints included progression-free survival (PFS), overall survival, duration of response (DoR), time to response (TTR), and time to progression (TTP). Investigator-assessed ORR was 53 % (n = 32, 95 % confidence interval (CI): 40.7–66.0) with the majority of patient responses demonstrating a PR (47 %). Four (7 %) patient responses demonstrated a CR, and ten (17 %) a stable disease. The median Kaplan–Meier estimate of investigator-assessed PFS, DoR, TTR, and TTP was 39.7 weeks (95 % CI 34.1–63.9), 48.7 weeks (95 % CI 31.7–57.1), 7.8 weeks (95 % CI 7.4–8.1), and 41 weeks (95 % CI 39.1–64.6), respectively. Lapatinib 1,000 mg with nab-paclitaxel 100 mg/m2 IV is feasible with manageable and predictable toxicity and an ORR of 53 % comparing favorably with other HER2-based combinations in this setting. 相似文献