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101.
Ng CF Koon CM Cheung DW Lam MY Leung PC Lau CB Fung KP 《Journal of ethnopharmacology》2011,137(3):1366-1372
Ethnopharmacological relevance
Radix Salviae miltiorrhizae (Danshen) and Radix Puerariae lobatae (Gegen) have long been used in traditional Chinese Medicine and serve as the principal herbs in treating cardiovascular disease.Aims of the study
In the present study, an aqueous extract comprising Danshen and Gegen in the ratio of 7:3 (DG) was investigated for its anti-hypertension in vivo and vasodilative activities ex vivo.Materials and methods
The anti-hypertensive effect of DG extract was investigated in spontaneously hypertensive rat (SHR) by measuring systolic blood pressure (SBP). Oral administration of DG extract was started at age of 6 weeks and 14 weeks for the preventive and therapeutic studies, respectively. Blood pressure was measured by tail-cuff method biweekly for 12 weeks. The ex vivo vasodilative activities of DG extract, its dependency on endothelium and the involvement of nitric oxide, prostacyclin and potassium channels were investigated using isolated rat aorta ring in organ bath.Results
For in vivo study, systolic blood pressure was significantly reduced in DG extract-treated groups (90.2 and 300 mg/kg) as compared with the SHR control in both preventive and therapeutic studies. However, DG extract was unable to suppress or delay the onset of hypertension in the preventive study. For ex vivo study, the results showed that DG extract induced a concentration-dependent relaxation in aorta and persisted response was observed with the removal of endothelium. Besides, pretreatment with a non-selective potassium channel inhibitor tetraethylammonium (TEA) also significantly inhibited DG extract-induced vasodilation. Further investigations on specific potassium channel blockers revealed that ATP-sensitive potassium (KATP) channel inhibitor glibenclamide, inward rectifier potassium (Kir) inhibitor barium chloride and voltage-dependent potassium (Kv) channel inhibitor 4-aminopyridine, but not BKCa channel inhibitor iberiotoxin, exerted significant inhibition on DG extract-induced vasodilation.Conclusions
The results of in vivo SHR animal model suggested that DG aqueous extract possessed blood pressure lowering effect on both pre- and post-hypertensive rats, which could be explained by its endothelium-independent vasodilation via the opening of KATP, Kir and Kv channels. 相似文献102.
Ethnopharmacological relevance
Species of Podocarpus are used traditionally in their native areas for the treatment of fevers, asthma, coughs, cholera, chest complaints, arthritis, rheumatism, venereal diseases and distemper in dogs.Aims of the study
To investigate the antioxidant, anti-inflammatory and anti-tyrosinase activities of four Podocarpus species, Podocarpus elongatus, Podocarpus falcatus, Podocarpus henkelii and Podocarpus latifolius, used in traditional medicine in South Africa. Phytochemical analysis to determine the phenolic contents was also carried out.Materials and methods
DPPH, FRAP and β-carotene-linoleic acid assays were used to determine the antioxidant/radical scavenging activities of these species. Anti-inflammatory activity of these species was assayed against two cyclooxygenase enzymes (COX-1 and COX-2). Tyrosinase inhibition activity was analysed using the modified dopachrome method with l-DOPA as the substrate. Phenolics were quantitatively determined using spectrophotometric methods.Results
Stems of Podocarpus latifolius exhibited the lowest EC50 (0.84 μg/ml) inhibition against DPPH. The percentage antioxidant activity based on the bleaching rate of β-carotene ranged from 96% to 99%. High ferric reducing power was observed in all the extracts. For COX-1, the lowest EC50 value was exhibited by stem extracts of Podocarpus elongatus (5.02 μg/ml) and leaf extract of Podocarpus latifolius showed the lowest EC50 against COX-2 (5.13 μg/ml). All extracts inhibited tyrosinase activity in a dose-dependent manner with stem extract of Podocarpus elongatus being the most potent with an EC50 value of 0.14 mg/ml. The total phenolic content ranged from 2.38 to 6.94 mg of GAE/g dry sample.Conclusion
The significant pharmacological activities observed support the use of these species in traditional medicine and may also be candidates in the search for modern pharmaceuticals in medicine, food and cosmetic industries. 相似文献103.
D Altavilla F Squadrito A Bitto F Polito BP Burnett V Di Stefano L Minutoli 《British journal of pharmacology》2009,157(8):1410-1418
Background and purpose:
The flavonoids, baicalin and catechin, from Scutellaria baicalensis and Acacia catechu, respectively, have been used for various clinical applications. Flavocoxid is a mixed extract containing baicalin and catechin, and acts as a dual inhibitor of cyclooxygenase (COX) and 5-lipoxygenase (LOX) enzymes. The anti-inflammatory activity, measured by protein and gene expression of inflammatory markers, of flavocoxid in rat peritoneal macrophages stimulated with Salmonella enteritidis lipopolysaccharide (LPS) was investigated.Experimental approach:
LPS-stimulated (1 µg·mL−1) peritoneal rat macrophages were co-incubated with different concentrations of flavocoxid (32–128 µg·mL−1) or RPMI medium for different incubation times. Inducible COX-2, 5-LOX, inducible nitric oxide synthase (iNOS) and inhibitory protein κB-α (IκB-α) levels were evaluated by Western blot analysis. Nuclear factor κB (NF-κB) binding activity was investigated by electrophoretic mobility shift assay. Tumour necrosis factor-α (TNF-α) gene and protein expression were measured by real-time polymerase chain reaction and enzyme-linked immunosorbent assay respectively. Finally, malondialdehyde (MDA) and nitrite levels in macrophage supernatants were evaluated.Key results:
LPS stimulation induced a pro-inflammatory phenotype in rat peritoneal macrophages. Flavocoxid (128 µg·mL−1) significantly inhibited COX-2 (LPS = 18 ± 2.1; flavocoxid = 3.8 ± 0.9 integrated intensity), 5-LOX (LPS = 20 ± 3.8; flavocoxid = 3.1 ± 0.8 integrated intensity) and iNOS expression (LPS = 15 ± 1.1; flavocoxid = 4.1 ± 0.4 integrated intensity), but did not modify COX-1 expression. PGE2 and LTB4 levels in culture supernatants were consequently decreased. Flavocoxid also prevented the loss of IκB-α protein (LPS = 1.9 ± 0.2; flavocoxid = 7.2 ± 1.6 integrated intensity), blunted increased NF-κB binding activity (LPS = 9.2 ± 2; flavocoxid = 2.4 ± 0.7 integrated intensity) and the enhanced TNF-α mRNA levels (LPS = 8 ± 0.9; flavocoxid = 1.9 ± 0.8 n-fold/β-actin) induced by LPS. Finally, flavocoxid decreased MDA, TNF and nitrite levels from LPS-stimulated macrophages.Conclusion and implications:
Flavocoxid might be useful as a potential anti-inflammatory agent, acting at the level of gene and protein expression. 相似文献104.
目的对云南兰坪地区带绦虫种类进行鉴定。方法选取成虫样本,进行基因组抽提,扩增线粒体细胞色素C氧化酶Ⅰ(mtCOXⅠ)部分基因片段,序列测定后,用生物学软件DNAMAN进行同源性分析并构建系统发育树。结果LP1和LP4同源性达99.8%,LP1-4与BZ2—3的同源性均在95%以上,而与BZ1的同源性较远,低于88%。亚洲带绦虫与牛带绦虫较接近,远离猪带绦虫。结论云南兰坪地区带绦虫株与亚洲带绦虫标准株相似,同属于亚洲带绦虫。mtCOXⅠ片段可用于带绦虫分类鉴定。 相似文献
105.
Pain that accompanies neuropathy is difficult to treat. Analgesics administered as monotherapies possess low activities in relieving this kind of pain.The effect of the simultaneous administration of indomethacin (a preferential inhibitor of cyclooxygenase-1; COX-1) or celecoxib (a relatively selective inhibitor of cyclooxygenase-2; COX-2), with selective antagonists of bradykinin2 (B2) bradykinin1 (B1) receptors (HOE 140 or des-Arg10-HOE 140) on the eleviation of diabetic and toxic neuropathic pain was investigated.Pretreatment with indomethacin (0.1 mg/kg, sc) increased the antihyperalgesic activity of low daily doses of HOE 140 or des-Arg10HOE 140 (70 nmol/kg, ip) in a diabetic (streptozotocin(STZ)-induced) neuropathy/hyperalgesia experimental model. Premedication with celecoxib before HOE 140 or des-Arg10HOE 140 administration resulted in a gradual reduction of STZ hyperalgesia. Furthermore, on days 23–24, almost complete abolishment of STZ hyperalgesia was observed. After cessation of drug administration, hyperalgesia quickly returned to the baseline threshold.The results of this study suggest that inhibitors of cyclooxygenases can increase the antihyperalgesic activity of selective antagonists of B2 and B1 receptors in diabetic and toxic neuropathic pain models. These observations may be clinically relevant. 相似文献
106.
107.
Many reports have demonstrated that non-steroidal anti-inflammatory drugs (NSAIDs) suppress malignant transformation and tumor growth, and some NSAIDs are expected to be new anti-cancer agents. In this study, we examined the anti-tumor effects of the non-specific cyclooxygenase (COX) inhibitors aspirin and piroxicam, and the selective COX-2 inhibitor meloxicam on xenotransplanted ovarian cancer. Tumor growth and survival were compared in female nu/nu mice, xenografted with subcutaneous OVCAR-3 tumors or with intraperitoneal DISS tumors and treated with aspirin (200 ppm in diet, everyday), piroxicam (150 ppm in diet, everyday) or meloxicam (162 ppm in diet, everyday). Al, of the agents tested significantly suppressed the growth of OVCAR-3 tumors xenotransplanted subcutaneously as compared to the control. There was a significant difference in inhibition of OVCAR-3 tumor growth between meloxicam and aspirin treatment. Meloxicam and piroxicam treatment significantly prolonged survival of mice with malignant ascites derived from DISS cells as compared to control and aspirin treatment. Mice treated with meloxicam survived significantly longer than those treated with piroxicam. There was no significant difference in survival between control and aspirin treatment. Necropsy revealed that one of the 6 cancer-bearing mice treated with piroxicam suffered from stomach perforation. These results indicate that a selective COX-2 inhibitor produces greater anti-tumor effect against ovarian cancer than a nonselective COX inhibitor and that meloxicam may have a potential of leading to a novel therapeutic strategy against ovarian cancer. 相似文献
108.
While it has been established that both the constitutive and inducible forms of cyclooxygenase (COX-1 and COX-2, respectively) play important roles in chemical initiation-promotion protocols with phorbol ester tumor promoters, the contribution of these two enzymes to ultraviolet (UV) light-induced skin tumors has not been fully assessed. To better understand the contribution of COX-1 and COX-2 to UV carcinogenesis, we transferred the null allele for each isoform onto the SKH-1 hairless strain of mouse. Due to low viability on this background with complete knockout of COX-2, heterozygous mice were used in UV carcinogenesis experiments. While the lack of one allele of COX-1 had no effect on tumor outcome, the lack of one allele of COX-2 resulted in a 50-65% reduction in tumor multiplicity and a marked decrease in tumor size. Additionally, transgenic SKH-1 mice that overexpress COX-2 under the control of a keratin 14 promoter developed 70% more tumors than wild-type SKH-1 mice. The lack of one allele of either COX-1 or COX-2 reduced prostaglandin (PG) E2 levels in response to a single UV treatment. The proliferative response to UV was significantly reduced in COX-2, but not COX-1, heterozygous mice. UV-induced apoptosis, however, was greater in COX-2 heterozygous mice. Collectively, these results clearly establish the requirement for COX-2 in the development of skin tumors. 相似文献
109.
110.
What is already known about this subject
- Paracetamol causes renal failure in overdose. Experimental studies have shown that paracetamol can inhibit COX II systemically in a manner similar to selective COX-II inhibitors.
- In overdose nonsteroidal anti-inflammatory drugs such as ibuprofen, cause dose-dependent increase in urinary potassium excretion (FeK) and sodium retention, probably due to vasoconstriction.
What this study adds
- Paracetamol overdose is associated with dose-related hypokalaemia and kaliuresis of short duration (<24 h), suggesting a specific renal effect of paracetamol in overdose.
- This effect seems likely to be via cyclo-oxygenase inhibition and may be separate from the nephrotoxic effects of paracetamol.