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81.
In order to evaluate the efficacy of and adverse reactions to terfenadine compared to dexchlorpheniramine, a double blind, group comparative study was carried out in 42 patients suffering from grass-pollen induced allergic rhinitis. The treatment was either terfenadine tablets 60 mg twice daily or dexchlorpheniramine tablets 6 mg twice daily. Nasal and eye symptoms as well as tiredness were rated daily on a scale from 0 (absent) to 3 (severe). Terfenadine and dexchlorpheniramine performed almost equally well in keeping symptoms at a mild level with a superiority of dexchlorpheniramine in the control of runny nose. Dexchlorpheniramine was associated with a significant increase in the score for tiredness in contrast to terfenadine which caused no significant change. Two patients in the group treated with dexchlorpheniramine stopped treatment because of tiredness. Other adverse reactions were few, mild and transient. 相似文献
82.
McNeela EA Jabbal-Gill I Illum L Pizza M Rappuoli R Podda A Lewis DJ Mills KH 《Vaccine》2004,22(8):909-914
We previously reported that intranasal immunization with a non-toxic mutant cross-reacting material (CRM)197 of diphtheria toxin, formulated with chitosan, generated protective neutralizing antibodies in mice and guinea pigs. Furthermore, we demonstrated that intranasal delivery of a powder formulation of the CRM197-based vaccine was well tolerated and significantly boosted antibody responses in adult volunteers. Here we report that intranasal booster immunization with CRM197 alone or with chitosan induced systemic T cell responses. We addressed for the first time the induction of T cell subtypes following intranasal vaccination in humans. Intranasal vaccination with CRM197, like parenteral immunization with a conventional diphtheria toxoid vaccine, enhanced antigen-specific IFN-gamma production. However, formulation of the nasal diphtheria vaccine with chitosan significantly augmented Th2-type responses, which correlated with protective levels of toxin-neutralizing antibodies in intranasally boosted individuals. The results suggest that vaccines capable of inducing strong Th2-type responses, such as CRM197 formulated with chitosan, have potential for the development of a protective mucosal vaccine against diphtheria in humans. Furthermore, our findings demonstrate that mucosal subunit vaccines with appropriate delivery systems have considerable potential for booster immunization of adults. 相似文献
83.
84.
Effect of a selected suppression of the reticuloendothelial system on the distribution of model carrier particles 总被引:1,自引:0,他引:1
The distribution of small labeled latex test particles has been studied after intravenous administration to the rabbit using the noninvasive technique of gamma scintigraphy. The reticuloendothelial system was suppressed using polystyrene latex particles and dextran sulfate as blocking agents. Both materials gave rise to significant uptake of particles in the lungs of the order of 60% of the administered dose. The effect seen with suppression with latex particles remained unaltered over an 8-d period, while for suppression with dextran sulfate the effect was transient, and particles that were initially deposited in the lungs were subsequently redistributed to the liver. The results are discussed in terms of previous studies on reticuloendothelial suppression using different agents, test colloids, and animal models. 相似文献
85.
S Charlton N S Jones S S Davis L Illum 《European journal of pharmaceutical sciences》2007,30(3-4):295-302
There is an increasing need to identify novel approaches by which to improve the efficiency of drug transport from the nasal cavity (olfactory region) to the CNS, especially for treatment of central nervous system disorders. It is suggested, that one approach is the combination of active targeting of a bioadhesive formulation, that will retain the drug at the absorption site, potentially in combination with, an absorption enhancer. Two low methylated pectins, LM-5 and LM-12 were selected for evaluation as drug delivery systems, due to their ability to gel in the nasal cavity and their bioadhesive characteristics, together with chitosan G210, which acts both as a bioadhesive material and as an efficient absorption enhancer. It was found that all of the bioadhesive formulations were able to reach the olfactory region in the nasal cavity of human volunteers when delivered using a simple nasal drop device. Furthermore, the formulations displayed a significantly increased residence time on the epithelial surface. This was in contrast to a non-bioadhesive control delivered with the same device. In contrast, a pectin formulation administered with a nasal spray system did not show an increase in residence time in the olfactory region. It was further shown that the reproducibility of olfactory delivery of a polymer formulation was significantly better intra-subject than inter-subject. 相似文献
86.
Is nose‐to‐brain transport of drugs in man a reality? 总被引:5,自引:0,他引:5
Illum L 《The Journal of pharmacy and pharmacology》2004,56(1):3-17
The blood-brain barrier that segregates the brain interstitial fluid from the circulating blood provides an efficient barrier for the diffusion of most, especially polar, drugs from the blood to receptors in the central nervous system (CNS). Hence limitations are evident in the treatment of CNS diseases, such as Parkinson's and Alzheimer's diseases, especially exploiting neuropeptides and similar polar and large molecular weight drugs. In recent years interest has been expressed in the use of the nasal route for delivery of drugs to the brain, exploiting the olfactory pathway. A wealth of studies has reported proof of nose-to-brain delivery of a range of different drugs in animal models, such as the rat. Studies in man have mostly compared the pharmacological effects (e.g. brain functions) of nasally applied drugs with parenterally applied drugs and have shown a distinct indication of direct nose-to-brain transport. Recent studies in volunteers involving cerebrospinal fluid sampling, blood sampling and pharmacokinetic analysis after nasal, and in some instances parenteral administration of different drugs, have in my opinion confirmed the likely existence of a direct pathway from nose to brain. 相似文献
87.
Tissue distribution of poly(hexyl 2-cyanoacrylate) nanoparticles coated with monoclonal antibodies in mice bearing human tumor xenografts 总被引:1,自引:0,他引:1
L Illum P D Jones R W Baldwin S S Davis 《The Journal of pharmacology and experimental therapeutics》1984,230(3):733-736
The tissue distribution of naked and either normal immunoglobulin G or monoclonal antibody (antitumor osteogenic sarcoma)-coated poly(hexyl-2-cyanoacrylate) nanoparticles was studied in mice bearing human tumor xenografts to evaluate the applicability of the systems for tumor targeting. All systems were shown to deposit mainly in the liver and spleen and no significant uptake was found in the tumors for either the naked or antibody-coated nanoparticles. 相似文献
88.
89.
P D Scholes A G Coombes L Illum S S Davis J F Watts C Ustariz M Vert M C Davies 《Journal of controlled release》1999,59(3):261-278
The surface chemical characterisation of sub-200 nm poly(DL-lactide co-glycolide) nanospheres has been carried out using the complementary analytical techniques of static secondary ion mass spectrometry (SSIMS) and X-ray photoelectron spectroscopy (XPS). The nanospheres, which are of interest for site-specific drug delivery, were prepared using an emulsification-solvent evaporation technique with poly(vinyl alcohol), Poloxamer 407 and Poloxamine 908 respectively as stabilisers. The presence of surfactant molecules on the surface of cleaned biodegradable colloids was confirmed and identified on a qualitative molecular level (SSIMS) and from a quantitative elemental and functional group analysis (XPS) perspective. SSIMS and XPS data were also used in combination with electron microscopy to monitor the effectiveness of cleaning procedures in removing poorly bound surfactant molecules from the surface of nanospheres. The findings are discussed with respect to the development of nanoparticle delivery systems, particularly the composition of the surface for extending blood circulation times and achieving site-specific deposition. 相似文献
90.
Proteins constitute an increasing proportion of the drugs in development. The barriers to their entry into the blood stream and rapid clearance means that they often have to be injected several times a day, affecting patient compliance. This paper reviews the major technologies enabling the development of injectable sustained-release products and formulation strategies to maintain protein integrity and modify release rates. Whilst many injectable sustained-release products are on the market, these are all delivering small molecular weight drugs and peptides. This is due to the manufacturing processes that denature and degrade the proteins upon encapsulation and release into the body. Formulation strategies are discussed and a number of new technologies reviewed that are able to overcome the issues with conventional manufacturing processes. The reliance of many processes on organic solvents has prevented their application to the development of injectable sustained release protein products. The development of entirely solvent free and aqueous methods of manufacture of these products has meant that numerous sustained-release protein products are close to reaching the market. 相似文献