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排序方式: 共有2149条查询结果,搜索用时 15 毫秒
1.
《药学学报(英文版)》2020,10(2):327-343
Our recent studies demonstrated that the natural product nobiletin (NOB) served as a promising multidrug resistance (MDR) reversal agent and improved the effectiveness of cancer chemotherapy in vitro. However, low aqueous solubility and difficulty in total synthesis limited its application as a therapeutic agent. To tackle these challenges, NOB was synthesized in a high yield by a concise route of six steps and fourteen derivatives were synthesized with remarkable solubility and efficacy. All the compounds showed improved sensitivity to paclitaxel (PTX) in P-glycoprotein (P-gp) overexpressing MDR cancer cells. Among them, compound 29d exhibited water solubility 280-fold higher than NOB. A drug-resistance A549/T xenograft model showed that 29d, at a dose of 50 mg/kg co-administered with PTX (15 mg/kg), inhibited tumor growth more effective than NOB and remarkably increased PTX concentration in the tumors via P-gp inhibition. Moreover, Western blot experiments revealed that 29d inhibited expression of NRF2, phosphorylated ERK and AKT in MDR cancer cells, thus implying 29d of multiple mechanisms to reverse MDR in lung cancer. 相似文献
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Tumor-associated macrophages (TAMs) are an important cause of tumorigenesis and tumor development. M2 macrophages can promote tumor growth while M1 macrophages kill tumor cells, therefore, polarizing macrophages to achieve a functional M1 phenotype could effectively play its anti-tumor role. In the current study, we synthesized a novel chrysin derivative which is termed as ChR-TD. And we found ChR-TD might be a ligand of TLR4 that polarized the TAMs towards M1 phenotype and played its anti-tumor role. Further study indicated that ChR-TD reprogrammed the macrophages into an M1 phenotype via TLR4 activation. Moreover, ChR-TD activated TLR4/NF-κB signaling pathway and promoted the NF-κB/p65 translocated into the nuclear, leading to the activation of NF-κB and proinflammatory cytokines release. In addition, type I interferon signaling was also activated by ChR-TD, leading to the expressions of IFN-α and IFN-β and its targeted genes NOS2, MCP-1 and IP-10 were significantly increased in macrophages. Importantly, these effects were disturbed in TLR4−/− macrophages, which are constructed by using CRISPR/Cas9 system. And the molecule docking simulation further indicated that ChR-TD could bind to TLR4 and might be a ligand of TLR4. Hence, these findings suggested that ChR-TD might be a ligand of TLR4 and can be used as a potential lead compound for tumors treatment. 相似文献
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Jirayut Euanorasetr Mayura Junhom Srisurang Tantimavanich Onanong Vorasin Bamroong Munyoo 《Journal of Asian natural products research》2016,18(5):462-474
Altholactone exhibited the anti-fungal activity with a high MIC value of 128 μg ml?1 against Cryptococcus neoformans and Saccharomyces cerevisiae. Fifteen ester derivatives of altholactone 1–15 were modified by esterification and their structures were confirmed by spectroscopic methods. Most of the ester derivatives exhibited stronger anti-fungal activities than that of the precursor altholactone. 3-Bromo- and 2,4-dichlorobenzoates (7 and 15) exhibited the lowest minimal inhibitory concentration (MIC) values against C. neoformans at 16 μg ml?1, while the 4-bromo-, 4-iodo-, and 1-bromo-3-chlorobenzoates (11–13) displayed potent activity against S. cerevisiae with MIC values of 1 μg ml?1. In conclusion, this analysis indicates that the anti-fungal activity of altholactone is enhanced by addition of halogenated benzoyl group to the 3-OH group. 相似文献
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The increasing use of illegal drugs by pregnant women causes a public health concern because it is associated with health risks for mothers and their developing children. One of such drugs is MDMA (3,4-methylenedioxymethamphetamine) or ecstasy due to its high consumption in relevant age and sex groups and its adverse effects on human and rodent developing brains. To thoroughly review the current knowledge on the developmentally neurotoxic potential of MDMA we systematically collected and summarized articles investigating developmental neurotoxicity (DNT) of MDMA in humans and animals in vivo and in vitro. In addition, we summarized the findings in a putative adverse outcome pathway (AOP). From an initial 299 articles retrieved from the bibliographic databases Web of Science, PubMed and DART, we selected 39 articles according to inclusion/exclusion criteria for data collection after title/abstract and full text screening. Of these 3 where epidemiological studies, 34 where in vivo studies in mice and rats and 2 were in vitro studies. The three epidemiological studies reported from the same longitudinal study and suggested that MDMA exposure during pregnancy impairs neuromotor function in infants. In rat, postnatal exposure towards MDMA also caused locomotor deficits as well as impaired spatial learning that might be associated with decreased serotonin levels in the hippocampus. In vitro MDMA caused cytotoxicity at high concentrations and effects on the serotonergic and neuritogenic alterations at lower concentrations which are in line with some of the in vivo alterations observed. Considering the adverse outcomes of developmental MDMA described in humans and in rodents we summarized the first putative AOP on developmental compound exposure leading to impaired neuromotor function in children. For generation of this AOP, MDMA exposure was taken as a model compound. In addition, we hypothesized a second AOP involving developmental disturbance of the dopaminergic system. However, further in vitro mechanistic studies are needed to understand the molecular initiating event(s) (MIE) triggering the downstream cascades and obtain consistent evidences causally linking the adverse outcome to effects at the cellular, organ and organism level. 相似文献
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The aim of this study was to characterize the stability of new vehicles for the undecylenoyl phenylalanine that is used as skin-lightening agent in the melasma treatment. The purpose of this research was also to analyse the release kinetics of phenylalanine derivative from topical preparations through different synthetic membranes. Topical formulations such as two different macroemulsions, hydrogels (based on carbomer and hydroxyethylcellulose) and microemulsions were characterized in terms of stability by laser diffraction method. Additionally, multiple light scattering assessed the stability of macroemulsions. The release rates of active substance through different membranes (such as Cuprophan, nitrocellulose, cellulose acetate and Strat-M) were determined using enhancer cell. In order to explain the mechanism of release process the results were fitted with different kinetic models. New stable vehicles for Ude-Phe were successfully obtained. The results proved that the membrane structure had the influence on the release rate of undecylenoyl phenylalanine. The slowest release rate of Ude-Phe was observed when Strat-M membrane was applied. The highest amount of active substance was released from the hydrogel based on carbomer. The release of undecylenoyl phenylalanine from both macroemulsions and hydrogel based on hydroxyethylcellulose followed the Higuchi model. Whereas the release results of Ude-Phe from both microemulsion-based hydrogels and carbomer hydrogel can be described by using Korsmeyer-Peppas model. Hydrogels and microemulsion-based hydrogels could be recommended as proper vehicles for the derivative of phenylalanine. 相似文献
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Protective effects of tanshinone IIA derivative on myocardial ischemia/reperfusion injury in rats 下载免费PDF全文
Wanli Shen Fei Yu Lu Xu Cong Chen Yini Cao Shu Liu Nanyin Han Chao Wang Rong Qi 《中国药学》2018,27(1):1-13
Tanshinone IIA (TSIIA) is the major bioactive constituent of Salvia miltiorrhiza Bunge, a Chinese herbal medicine, which has protective effects on myocardial ischemia/reperfusion (MIR) injury. However, the cardioprotective effects of TSIIA as well as its clinical use were limited due to its poor water solubility. The objective of this study was to evaluate whether Tanshinone IIA derivative (TD), a new water soluble compound synthesized by TSIIA and N-Methyl-D-Glucamine, had protective effects on MIR injury and what the related mechanism was. The cardioprotective effects of TD were evaluated and compared with TSIIA in a rat MIR model. The results show that pretreatment with TD significantly alleviated inflammatory infiltration and exhibited antioxidant effect in MIR injury by reducing the activity of lactate dehydrogenase (LDH) and malondialdehyde (MDA), decreasing expression of nuclear factor-κ-gene binding (NF-κB) and upregulating expression of heme oxygenase (HO-1), but having no effect on the content of total superoxide dismutase (T-SOD) and mRNA expression of superoxide dismutase (SOD-1). Thus, our study reveals that TD exerted significant protective effects on MIR injury through attenuating oxidative stress and inflammatory responses. 相似文献
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S. Anil MDS V. T. Beena MDS † Ravindran Ankathil MSc PhD ‡ P. Remani MSc PhD § T. Vijayakumar MSc PhD ¶ 《Australian dental journal》1995,40(1):39-42
A case of mandibulofacial dysostosis (Treacher Collins syndrome) is presented. Clinical features and skull radiographs revealed typical anomalies associated with the syndrome. Cleft of the soft palate and unerupted multiple supernumerary teeth were present in this case. No haematological, biochemical or immunological abnormalities could be detected in the patient. Pedigree analysis showed an autosomal dominant mode of transmission of the disease. Chromosomal studies did not reveal any structural or numerical discrepancies. 相似文献