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1.
目的 观察米诺环素对压力系统作用下大鼠视网膜神经细胞(RNs)的活性及凋亡的影响,探讨其对受损RNs保护的可能机制。 方法 制备大鼠RNs体外加压培养模型,通过细胞形态学观察、四唑盐(MTT)比色法测定细胞活力、吖啶橙/溴化乙锭(AO/EB)染色法检测细胞凋亡率等方法观察不同浓度的米诺环素对上述损伤细胞的保护作用,并用免疫细胞化学法观察iNOS和caspase 3表达的改变。 结果 加压培养后RNs与对照组相比形态改变较明显,细胞活力降低,5393%的细胞发生凋亡。20000 μmol/L的米诺环素治疗组则细胞形态改善,活力显著增高,1729%的细胞发生凋亡;免疫细胞化学法显示细胞内iNOS和caspase-3表达较加压损伤组减少。 结论 一定剂量的米诺环素在体外可有效抑制压力引起的大鼠RNs损伤及凋亡;抑制iNOS和caspase-3的表达可能是其潜在作用机制。 相似文献
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利用反相高效液相色谱法测定二甲胺四环素含量,该法使用200×5mm内径的色谱柱,内装YWG-C18H37。,柱温25±0.5℃,流动相为0.002mol/L EDTA-Na2溶液(用草酸调节pH3.0±0.1):甲醇:乙腈(3:1:1V/V/V),流速为1ml/min,紫外检测波长为280um,测定了15批国内外厂家生产的二甲胺四环素联囊的含量,结果与用美国药典(22版)法所测结果一致。 相似文献
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Masakazu Yamagata Kimiko Kumano Masato Ueda 《Journal of the European Academy of Dermatology and Venereology》1997,9(3):256-258
Pyoderma gangrenosum is a rare, chronic, inflammatory ulcerative skin disease of unknown etiology and pathogenesis. It is often associated with systemic disease. We describe a patient with pyoderma gangrenosum associated with ulcerative colitis and aseptic abscesses of the subcutis and spleen, which have been rarely reported previously. These manifestations were cleared by combined therapy with minocycline hydrochloride and diaphenylsulfone. 相似文献
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In vitro synergistic effect of minocycline combined with antifungals against Cryptococcus neoformans
Lihua Tan Haiyan Shi Mei Chen Zikuo Wang Zhaoqian Yao Yi Sun 《Journal de Mycologie Médicale》2022,32(1):101227
BackgroundCryptococcus neoformans infections occur in immunocompromised patients, especially those with HIV infection, chemoradiotherapy after cancer, and organ transplantation. Infection can cause pneumonia and meningoencephalitis in severe cases with a high mortality rate if not treated. Although fluconazole and amphotericin B are the first-line treatments for cryptococcosis, the rate of fluconazole resistance has increased significantly due to long-term use. Minocycline is a derivative of tetracycline that exerts its antibacterial effect through inhibition of bacterial protein synthesis. It is also able to pass the blood-brain barrier to act on the central nervous system. The present study investigates the effects of minocycline in combination with antifungals in treating C. neoformans.ObjectiveTo determine in vitro interactions of minocycline combined with itraconazole, voriconazole, posaconazole, fluconazole and amphotericin B against C. neoformans.MethodsThe minimum inhibitory concentrations (MIC) of the antifungals were determined by the CLSI Clinical and Laboratory Standards Institute M27-A3 microdilution method. The in vitro synergistic effects of minocycline combined with itraconazole, voriconazole, posaconazole, fluconazole, and amphotericin B on C. neoformans were detected by the broth microdilution checkerboard technique and disk diffusion testing.Results and ConclusionThe working concentration ranges were 0.125–4 µg/mL for itraconazole, 0.03–0.125 µg/ml for voriconazole, 0.03–1 µg/ml for posaconazole, 0.25–16 µg/ml for fluconazole, and 0.125–2 µg/ml for amphotericin B. The synergistic rates of minocycline combinations against C. neoformans were 55% with itraconazole, 10% with voriconazole, 85% with posaconazole, 20% with fluconazole, and 70% with amphotericin B. The effective MIC value of minocycline in the synergistic combination decreased to 2–32 µg/ml, while the MIC of itraconazole decreased to 0.03–0.125 µg/ml, voriconazole 0.03–0.125 µg/ml, posaconazole 0.03–0.125 µg/ml, 0.125–4 µg/ml fluconazole, and 0.06–0.50 µg/ml amphotericin B. The disk diffusion assay showed that the plates containing minocycline and antifungal drugs produced inhibition zones with diameters larger than the single drug plates. Minocycline showed no antagonistic effect in the combinations. In conclusion, the combination of minocycline and azoles or amphotericin B has synergistic effects against C. neoformans in vitro. 相似文献
6.
The tetracycline analogs minocycline and doxycycline inhibit angiogenesis in vitro by a non-metalloproteinase-dependent mechanism 总被引:4,自引:0,他引:4
S. Gilbertson-Beadling E. A. Powers M. Stamp-Cole P. S. Scott T. L. Wallace J. Copeland G. Petzold M. Mitchell S. Ledbetter R. Poorman J. W. Wilks C. Fisher 《Cancer chemotherapy and pharmacology》1995,36(5):418-424
The tetracycline analogs minocycline and doxycycline are inhibitors of metalloproteinases (MMPs) and have been shown to inhibit angiogenesis in vivo. To further study the mechanism of action of these compounds we tested them in an in vitro model of angiogenesis: aortic sprouting in fibrin gels. Angiogenesis was quantitated in this system by a unique application of planar morphometry. Both compounds were found to potently inhibit angiogenesis in this model. To further characterize the activity of these compounds against MMPs, we determined the IC50s of both compounds against representatives of three classes of metalloproteinases: fibroblast collagenase, stromelysin, and gelatinase A. Doxycycline was found to inhibit collagenase, gelatinase A and stromelysin with IC50s of 452 M, 56 M and 32 M, respectively. Minocycline was found to inhibit only stromelysin in the micromolar range with an IC50 of 290 M. Since these results suggest that these compounds may not have been inhibiting in vitro angiogenesis by an MMP-dependent mechanism, we decided to test the effects of the potent MMP inhibitor BB-94. This compound failed to inhibit aortic sprouting in fibrin gels, thus strongly suggesting that both doxycycline and minocycline act by an MMP-independent mechanism. These results have implications for the mechanism of action of tetracycline analogs, particularly where they are being considered for the treatment of disorders of extracellular matrix degradation including periodontal disease, arthritis, and tumor angiogenesis. 相似文献
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《The Foot》2016
Black bone disease has been recognised as a potential consequence of long-term treatment with tetracycline antibiotics. Largely documented affecting structures in the head and skull, there are few reported cases of black bone disease in the foot and ankle. The case of a 55 years old patient, who as a teenager, had undergone treatment with minocycline hydrochloride for chronic acne, and was found to have bone discolouration consistent with minocycline induced black bone disease (MIBBD) during the course of hallux valgus corrective surgery some 40 years later, is presented. In spite of the intraoperative findings, the patient’s post-operative recovery and bone healing was uneventful. The literature on minocycline induced black bone disease is reviewed. 相似文献
9.
BackgroundOur previous study reports the causal role of high mobility group box 1 (HMGB1) in the development of depression; and we find glycyrrhizic acid (GZA) can be a potential treatment for major depressive disorder (MDD) considering its inhibition of HMGB1 activity. This study aims to further explore the exact cell types that release HMGB1 in the hippocampus.MethodsWe detected the effects of microglia conditioned medium on primary astrocytes and neurons. The effects of minocycline on depressive-like behaviors were tested in BABLB/c mice after four weeks of chronic unpredictable mild stress (CUMS) exposure. Furthermore, the immunofluorescence (IF) assays, hematoxylin-eosin (HE) and TUNEL staining were used to observe hippocampal slices to evaluate the release of HMGB1. The cytoplasmic translocations of HMGB1 protein were assayed by western-blot.ResultsExposure to CUMS caused an active release of HMGB1 from microglia and neurons in the hippocampus. After minocycline administration for inhibiting the activation of microglia, both microglia and neurons reduced the release of HMGB1 and the protein level of central and peripheral HMGB1 recovered accordingly. Along with blocking the release of HMGB1, behavioral and cognitive deficits induced by CUMS were improved significantly by minocycline. In addition, the supernatant of primary microglia stimulated the secretion of HMGB1 in primary neurons, not in astrocytes, at 24 h after 4 h-LPS treatment.ConclusionAll the evidence supported our hypotheses that microglia and neurons are the main cell sources of HMGB1 release under CUMS condition, and that the release of HMGB1 by microglia may play an important role in the development of depressive-like behavior. 相似文献
10.
目的观察米诺环素(Minocycline,MN)对缺氧缺血脑损伤(hypoxic-ischemic brain damage,HIBD)未成熟新生大鼠Toll样受体4(Toll-1ike receptor4,TLR4)、核因子-κB(nuclear factor-kappa B,NF—κB)p65和TNF.仪表达的影响,探索米诺环素脑保护作用机制。方法将160只生后2d(P2)Sprague—Dawley(SD)新生大鼠随机分成正常对照组、假手术组、HIBD组、HIBD加MN组。通过结扎左侧颈总动脉及8%氮氧混合气缺氧4h,制备未成熟新生大鼠缺氧缺血性脑损伤模型。HIBD加MN组大鼠缺氧后予腹腔注射1次MN45mg/kg,HIBD组予腹腔注射等剂量的无菌PBS(pH7.4)。HI后24h、48h、72h取材,Westernblotting检测TLR4、NF.KBp65和TNF—Ot蛋白表达,HI后72h、4周行脑组织HE染色及病理评分,HI后4周行行为学检测。结果HI后72h、4周HIBD加MN组脑组织病理损伤较HIBD组减轻,HIBD加MN组半定量病理评分低于HIBD组,差异有统计学意义(P〈0.05)。Western blotting显示HI后24、48和72hHIBD加MN组TLR4、NF—KBp65和TNF-α的表达低于HIBD组,较正常组及假手术组升高。HI后4周,在悬吊试验及斜坡试验中,HIBD加MN组与正常组、假手术组差异无统计学意义(Jp〉0.05)。旷场试验中,HIBD加MN组与正常组、假手术组对比,差异有统计学意义(P〈0.05);与HIBD组比较,P=0.375,差异无统计学意义(P〉O.05)。圆筒实验中HIBD加MN组左侧上肢触壁百分比较HIBD组降低(P〈0.05),与正常组、假手术组差异无统计学意义(P〉0.05);右侧触壁百分比的比较中,HIBD加MN组与正常组、假手术组、HIBD组差异无统计学意义(P〉0.05)。结论米诺环素对缺氧缺血脑损伤近期及远期具有良好的保护作用,其对缺氧缺血脑损伤的保护作用机制可能与抑制TLR4.NF—κBp65-TNF-α信号途径的激活有关。 相似文献