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81.
82.
Biodegradable poly(epsilon -caprolactone) nanoparticles for tumor-targeted delivery of tamoxifen 总被引:7,自引:0,他引:7
To increase the local concentration of tamoxifen in estrogen receptor (ER) positive breast cancer, we have developed and characterized nanoparticle formulation using poly(epsilon -caprolactone) (PCL). The nanoparticles were prepared by solvent displacement method using acetone-water system. Particle size analysis, scanning electron microscopy, zeta potential measurements, and differential scanning calorimetry (DSC) were used for nanoparticle characterization. Biodegradation studies were performed in the presence and absence of Pseudomonas lipase in phosphate-buffered saline (PBS, pH 7.4) at 37 degrees C. Tamoxifen loading over different concentrations was analyzed by high-performance liquid chromatography (HPLC) and the optimum loading concentration was determined. In vitro release studies were performed in 0.5% (w/v) sodium lauryl sulfate (SLS) containing PBS at 37 degrees C. Cellular uptake and distribution of fluorescent-labeled nanoparticles was examined in MCF-7 breast cancer cells. SEM micrographs and Coulter analysis showed nanoparticles with spherical shape and uniform size distribution (250-300 nm), respectively. Zeta potential analysis revealed a positive surface charge of +25 mV on the tamoxifen-loaded formulation. Being hydrophobic crystalline polyester, PCL did not degrade in PBS alone, but the degradation was enhanced by the presence of lipase. The maximum tamoxifen loading efficiency was 64%. Initial burst release of tamoxifen was observed, probably due to significant surface presence of the drug on the nanoparticles. A large fraction of the administered nanoparticle dose was taken up by MCF-7 cells through non-specific endocytosis. The nanoparticles were found in the perinuclear region after 1 h. Results of the study suggest that nanoparticle formulations of selective ER modulators, like tamoxifen, would provide increased therapeutic benefit by delivering the drug in the vicinity of the ER. 相似文献
83.
Nazzal S Smalyukh II Lavrentovich OD Khan MA 《International journal of pharmaceutics》2002,235(1-2):247-265
The objectives of the present work were, first, to develop a self-nanoemulsified drug delivery system (SNEDDS) based on the eutectic properties of ubiquinone (CoQ10); and second, to study the progress of emulsion formation and drug release mechanisms by turbidimetry and droplet size analysis. Binary phase diagrams of CoQ10 with menthol and essential oils were constructed and used to develop the self-nanoemulsified formulation. Pseudo ternary phase diagram was constructed to identify the efficient self-emulsification region. Release mechanisms of the resultant formulas were quantified using turbidimetry in combination with dissolution studies. Turbidity time profiles revealed three distinctive regions: lag phase, plateau, and the pseudolinear phase. Lag phase was attributed to the liquid crystalline properties of the formula. Plateau turbidity was correlated with droplet size. Laser diffraction analysis revealed an average droplet diameter of 100 nm. Emulsification rate was obtained from the corrected slope of the pseudolinear phase of the profile. Stability of the formula was further evaluated using Fourier transform-infrared (FT-IR) attached to an attenuated total reflectance (ATR) accessory. The present study revealed a eutectic based semisolid self-emulsified delivery system that can overcome the drawbacks of the traditional emulsified systems such as low solubility and irreversible precipitation of the active drug in the vehicle with time. 相似文献
84.
The main objective of the study was to develop a stomach-specific drug delivery system to increase the efficacy of tetracycline against Helicobacter pylori. Chitosan microspheres were prepared by ionic cross-linking and precipitation with sodium sulfate. Two different methods were used for drug loading. In method I, tetracycline was mixed with chitosan solution before the simultaneous cross-linking and precipitation. In method II, the drug was incubated with pre-formed microspheres for 48 h. The cumulative amount of tetracycline that was released from chitosan microspheres and the stability of the drug was examined in different pH medium at 37 degrees C. Microspheres with a spherical shape and an average diameter of 2.0-3.0 microm were formed. When the drug was added to the polymer solution before cross-linking and precipitation only 8% (w/w) was optimally incorporated in the final microsphere formulation. When the drug was incubated with the pre-formed microspheres, on the other hand, a maximum of 69% (w/w) could be loaded. Thirty percent of tetracycline either in solution or when released from microspheres was found to degrade at pH 1.2 in 12 h. The preliminary results from this study suggest that chitosan microspheres can be used to incorporate antibiotic drugs and may be effective when administered locally in the stomach against H. pylori. 相似文献
85.
Oral delivery of proteins: progress and prognostication 总被引:1,自引:0,他引:1
The delivery of proteins has gained momentum with the development of biotechnology sector that provided large-scale availability of therapeutic proteins. The availability is mostly due to the advances in recombinant DNA technology. The low oral bioavailability, however, continues to be a problem for several proteins because of their large molecular size, low permeation through biological membranes, and susceptibility to molecular changes in both biological and physical environments. The demand for effective delivery of proteins by the oral route has brought a tremendous thrust in recent years both in the scope and complexity of drug delivery technology. The important therapeutic proteins and peptides being explored for oral delivery include insulin, calcitonin, interferons, human growth hormone, glucagons, gonadotropin-releasing hormones, enkephalins, vaccines, enzymes, hormone analogs, and enzyme inhibitors. This article reviews the progress in oral delivery of these proteins, provides comments on the strategies to improve their oral bioavailability, and highlights their current market trends. 相似文献
86.
Intratumoral administration of paclitaxel in an in situ gelling poloxamer 407 formulation 总被引:6,自引:0,他引:6
In order to examine the efficacy of paclitaxel (Taxol, Bristol-Myers Squibb) after administration locally at the tumor site, we have developed a thermo-reversible gelling formulation in poloxamer 407 (Pluronic F-127) solution. Paclitaxel was incorporated in poloxamer 407 [20% (w/w)] at 0.5- and 1.0-mg/mL concentrations. The in vitro release studies were carried out in phosphate-buffered saline (pH 7.4) at 37 degrees C. Control and paclitaxel-poloxamer 407 formulations were administered intratumorally at a dose of 20 mg/kg in B16F1 melanoma-bearing mice. The change in tumor volume as a function of time and the survival of treated animals were used as measures of efficacy. Poloxamer 407 solution undergoes a reversible sol-gel transition when the temperature is raised to above 21 degrees C. In vitro paclitaxel release from poloxamer 407 gels was very slow (only 6.1% after 6 hr) probably due to the poor aqueous solubility of the drug. Significant enhancement in the anti-tumor efficacy was noted following intratumoral administration of paclitaxel-poloxamer 407 formulation. The initial tumor growth rate was delayed by 67% and the tumor volume doubling time was increased by 72% relative to saline control. In addition, more than 91% of the tumor-bearing animals that received paclitaxel in poloxamer 407 gel survived on day 15 post-administration as compared to 58% in the control group. The results of this study show significant benefit of paclitaxel for solid tumor when administered locally in an in situ gelling poloxamer 407 formulation. 相似文献
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89.
Apeland T Mansoor MA Pentieva K McNulty H Seljeflot I Strandjord RE 《Epilepsy research》2002,51(3):237-247
Patients on antiepileptic drugs (AEDs) may have elevated levels of plasma total homocysteine (p-tHcy). The aim of this study was to assess the effect of B-vitamin supplementation on the levels of p-tHcy and markers of endothelial activation and lipid peroxidation. A total of 33 adult patients on AEDs were identified with either fasting (Group 1, n=23) or post methionine load (PML) (Group 2, n=10) hyperhomocysteinemia. Subjects were supplemented with B-vitamins for 30 days: folic acid 0.4 mg, pyridoxine 120 mg and riboflavin 75 mg per day. After supplementation, serum folate and pyridoxal phosphate had increased, while fasting and PML p-tHcy had decreased (P<0.0001) by 36 and 26%, respectively. Prior to supplementation, the Group 1 patients had elevated levels of P-selectin and von Willebrand factor (vWF) (P=0.05 and 0.03, respectively). After supplementation, the levels of intercellular cell adhesion molecules had decreased (P=0.01) and E-selectin decreased nonsignificantly (P=0.07). However, the levels of vascular cell adhesion molecules had increased (P<0.0001), while lipid peroxidation were unchanged. In conclusion, the combined supplementation with folic acid, pyridoxine and riboflavin reduced fasting and PML hyperhomocysteinemia in patients on AEDs. Patients with fasting hyperhomocysteinemia had elevated levels of P-selectin and vWF, which may indicate an increased risk of cardiovascular disease. Furthermore, B-vitamin supplementation influenced endothelial activation, although the clinical implication is uncertain. 相似文献
90.
Voltage-gated potassium ion channels in colon cancer 总被引:6,自引:0,他引:6
Voltage-gated potassium channels (VGPCs) have been previously implicated in cellular proliferation. In this study, the expression of VGPCs was examined by immunohistochemistry in seventy-four human colonic carcinoma specimens. Immunostaining for the Kv1.3 type VGPC was absent in two normal human colon specimens. Kv1.3 staining in the 74 colon cancer specimens was low in 9% (7/74), moderate in 61% (45/74) and high in 30% (22/74). Potassium channel (PC) openers, minoxidil and diazoxide (5-50 microg/ml), increased growth of SW1116, LoVo, Colo320DM and LS174t human colon cancer cell lines by 20-40%. PC-blockers, dequalinium and amiodarone, caused marked growth-inhibition of the four cell lines, at concentrations between 1 to 3 microg/ml. PC-blockers such as glibenclamide inhibited cellular proliferation at concentrations above 50 microg/ml while tetraethylammonium and 4-aminopyridine (up to 100 microg/ml) did not have significant growth-suppressive effects. Our results indicate the presence of VGPCs in colon cancer and suggest that PCs could serve as therapeutic targets. 相似文献