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1.
Treatment of posterior eye diseases is more challenging than the anterior segment ailments due to a series of anatomical barriers and physiological constraints confronted by drug delivery to the back of the eye. In recent years, concerted efforts in drug delivery have been made to prolong the residence time of drugs injected in the vitreous humor of the eye. Our previous studies demonstrated that poly(ortho ester) (POE) nanoparticles were biodegradable/biocompatible and were capable of long-term sustained release. The objective of the present study was to investigate the safety and localization of POE nanoparticles in New Zealand white rabbits and C57BL/6 mice after intravitreal administration for the treatment of chronic posterior ocular diseases. Two concentration levels of POE nanoparticles solution were chosen for intravitreal injection: 1.5?mg/ml and 10?mg/ml. Our results demonstrate that POE nanoparticles were distributed throughout the vitreous cavity by optical coherence tomography (OCT) examination 14 days post-intravitreal injection. Intraocular pressure was not changed from baseline. Inflammatory or adverse effects were undetectable by slit lamp biomicroscopy. Furthermore, we demonstrate that POE nanoparticles have negligible toxicity assessed at the cellular level evidenced by a lack of glia activation or apoptosis estimation after intravitreal injection. Collectively, POE nanoparticles are a novel and nontoxic as an ocular drug delivery system for the treatment of posterior ocular diseases. 相似文献
2.
AbstractCadmium (Cd) as environmental pollutant can induce severe damage, particularly to the testis. This study investigated the effects of Caffeic acid phenethyl ester (CAPE) on testicular dysfunction induced by Cd. Adult mice were intraperitoneally injected with cadmium chloride (CdCl2) with different doses of CAPE pretreatment. After CdCl2 injection, body/testis weight ratio decreased, Cd levels accumulated and zinc levels decreased in testis. Furthermore, Cd intoxication caused a significant increase of oxidative stress levels, antioxidant enzymes activities, and glutathione levels. Interestingly, significant improvements were observed after the administration of CAPE. Our results demonstrated the protective effect of CAPE, linking Cd testicular dysfunction to oxidative stress. 相似文献
3.
Neurotransmitter- or neuromodulator-like actions ofl-DOPA were investigated with intracellular recordings from submucous plexus neurons of the guinea-pig caecum.l-DOPA at 30 nM augmented the amplitude of fast EPSPs, but did not affect depolarizations elicited by puff application of acetylcholine (ACh). The augmenting effect ofl-DOPA on the fast EPSPs was counteracted byl-DOPA methyl ester. The fast EPSPs were depressed by 10 μMl-DOPA, but transiently augmented after rinsing the drug.l-DOPA methyl ester did not affect the inhibitory action ofl-DOPA on the fast EPSPs, but antagonized the potentiation following the inhibition. The depolarization elicited by exogenously applied. ACh was inhibited by 10 μMl-DOPA. Intracellular Ca2+ concentrations ([Ca2+]i) of the neuronal soma were measured with fura-2 microfluorophotometry. The transient increase in the [Ca2+]i evoked by the somatic action potential (Δ[Ca2+]AP) was facilitated by 30 nMl-DOPA, but decreased by the drug at 10 μM. It is concluded thatl-DOPA at low concentrations enhances the Δ[Ca2+]AP, increasing the neurotransmitter release, but at high dose diminishes the Δ[Ca2+]AP, inhibiting the neurotransmission. 相似文献
4.
Francesca Borrelli Nicola Borbone Raffaele Capasso Domenico Montesano Simona De Marino Gabriella Aviello Giovanni Aprea Stefania Masone Angelo A. Izzo 《Journal of ethnopharmacology》2009
Ethnopharmacological importance
Celastrus paniculatus Willd. (Celastraceae) is an Ayurvedic remedy used for the treatment of a number of diseases, including bowel spasms.Aim of the study
To investigate the mode of the relaxing action of a methanolic extract prepared from the seeds of Celastrus paniculatus (CPE, 0.0001–10 μg/mL) in the rat ileum and to try to confirm on human tissues the intestinal pharmacological activity of the extract.Materials and methods
The relaxant effect of CPE was studied in vitro by evaluating its effect on the spontaneous contractions of the isolated ileum.Results
CPE exerted a tetrodotoxin- and ω-conotoxin-resistant inhibitory effect on rat ileum motility (IC50: 0.24 ± 0.02 μg/mL; Emax: 99.0 ± 0.60%). The inhibitory effect was reduced by nifedipine but not by cyclopiazonic acid. Experiments with specific antagonists enabled us to exclude the involvement of the main endogenous spasmogenic (i.e. acetylcholine and tachykinins) and relaxing (noradrenaline, nitric oxide, ATP) compounds. CPE also relaxed the isolated human ileum (IC50: 0.26 ± 0.02 μg/mL; Emax: 99.1 ± 0.46%).Conclusion
It is concluded that (i) CPE exerted a powerful myogenic and L-type Ca2+-dependent relaxing effect in the isolated rat ileum and that (ii) the human ileum is sensitive to the inhibitory effect of CPE. If confirmed in vivo, our data could explain the traditional use of this herb in the treatment of intestinal spasms. 相似文献5.
R. Alan Aitken Michael C. Bibby John A. Double Andrea L. Laws Robert B. Ritchie David W. J. Wilson 《Archiv der Pharmazie》1997,330(7):215-224
A range of 18 derivatives of flavone-8-acetic acid (FAA) with substituents on the 2-phenyl group have been prepared and their anti-tumour activity evaluated in vitro against a panel of human and murine tumour cell lines and in vivo against MAC 15A. There was no clear-cut relationship between in vitro and in vivo activity but the activity in each situation was found to be very sensitive to the precise substitution pattern with closely related isomers giving widely different activities. Some of the compounds, notably 10b,cj , and r , were active in vivo and these require further studies in order to evaluate their potential for development. 相似文献
6.
Sarabjit S. Neelam Alvise Bernabei Curtis Freedland Roxanna Thompson Thomas H. Corbett Gordon D. Luk 《Investigational new drugs》1990,8(3):263-268
Summary Unresectable solid tumors in the metastatic stage are quite resistant to current chemotherapy and radiation therapy regimens. Flavone acetic acid (FAA) is a novel antitumor agent which appears to work through a different mechanism than the conventional chemotherapeutic agents. In preclinical studies it has shown effectiveness against a variety of transplantable murine and human tumors and appears to be solid tumor selective. It also has non-overlapping toxicities as compared to conventional agents. We therefore investigated FAA in vitro against human colon cancer cells and explored whether its effectiveness could be enhanced in combination with other agents such as adriamycin (ADR), cis-platinum (CP) and difluoromethyornithine (DFMO) — an inhibitor of polyamine biosynthesis. Addition of FAA for 24 hours in liquid media produced dose dependent growth inhibition. Using soft agar colony assay, growth was inhibited by 58% by 3mM FAA and only 1.4% by 0.375mM FAA. The combination of FAA and cis-platinum produced synergism at the lower doses tested. The combination of FAA and adriamycin produced antagonism at all doses tested and the combination of FAA with DFMO did not produce results significantly different from DFMO alone. We conclude that enhancement of FAA activity can be achieved in combination with conventional antitumor agents, but may be drug and dose specific. 相似文献
7.
为证明癫痫发作早期一氧化氮(NO)抗发作效应,用NO合酶(NOS)抑制剂L-硝基精氨酸甲酯(L-NAME)对大鼠红藻氨酸(KA)诱导性发作进行干预,同时用分光光度法检测海马结构中NOS活性的早期变化。发现KA发作10min、30min组海马结构中NOS活性明显升高,而KA注射前30min给予L-NAME可显著抑制NOS活性的升高,这种抑制效应与大鼠KA发作中湿狗样摇动(WDS)的提早出现和发生次数增多显著相关。结果提示在KA诱导大鼠发作早期内源性NO具有明显的抗发作效用。 相似文献
8.
采用薄层扫描法对复脉定冲剂中远志有效成分3,4,5-三甲氧基反式肉桂酸乙酯的含量进行测定。方法简单、快速,结果可靠,可作为该制剂的质控标准。 相似文献
9.
青黛颗粒抗炎、镇痛作用的实验研究 总被引:3,自引:0,他引:3
目的 :通过对青黛颗粒抗炎、镇痛作用的实验研究 ,探讨该药治疗溃疡性结肠炎的作用机理。方法 :采用小鼠醋酸扭体法、大鼠棉球肉芽肿法和角叉菜胶所致大鼠足肿胀方法。结果 :青黛颗粒给药高、中、低剂量组和阳性对照药组均明显降低小鼠扭体次数 (P<0 .0 5~P<0 .0 1)。对大鼠棉球肉芽肿和大鼠足肿胀有显著的抑制作用 (P <0 .0 1~P <0 .0 0 1)。结论 :青黛颗粒分别对大鼠具有抗炎、对小鼠具有镇痛作用。且镇痛作用呈量效关系 相似文献
10.
维胺酯-β-环糊精包合物的研究 总被引:6,自引:0,他引:6
应用3因素8水平的均匀设计方法,优化出维胺酯-β-环糊精包合物最佳制备条件,所得包合物的包合率为99.3%,其表观稳定常数为1394M-1. 相似文献