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991.
Xiao-chang LIU Qiao MEI Jian-ming XU Jing HU 《中国药理学报》2009,(7):987-993
Aim: To investigate the effect of balsalazine treatment on intestinal mucosal permeability in dextran sulfate sodium (DSS)-induced colitis and to determine the mechanism of the balsalazine-induced changes.
Methods: Experimental colitis was induced in C57BL/6J mice by the administration of 5% DSS. Balsalazine was administered intragastrically at doses of 42, 141, and 423 mg/kg. The disease activity index (DAI) score was evaluated and colon tissue was collected for the assessment of histological changes. The amount of malondialdehyde (MDA) in the colon was determined, along with the activity of myeloperoxidase (MPO), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Mucosa from the small intestine was collected to determine the levels of tumor necrosis factor (TNF)-α and interferon (IFN)-γ. The mucosa was ultrastructurally examined with transmission electron microscopy and intestinal permeability was assayed using Evans blue.
Results: Balsalazine was found to reduce the DAI score and the histological index (HI) score, decrease the MDA content and the activity of MPO, and increase the activity of SOD and GSH-Px in colitis mice. At the same time, balsalazine ameliorated microvillus and tight junction structure, resulting in a decrease in the amount of Evans blue permeating into the intestinal wall and the levels of TNF-α and IFN-γ in colitis mice.
Conclusion: In colitis mice, the anti-colitis effect of balsalazine results in a decrease in intestinal mucosal permeability. The mechanism of this effect is partly associated with balsalazine's antioxidative and anti-inflammatory effects. 相似文献
Methods: Experimental colitis was induced in C57BL/6J mice by the administration of 5% DSS. Balsalazine was administered intragastrically at doses of 42, 141, and 423 mg/kg. The disease activity index (DAI) score was evaluated and colon tissue was collected for the assessment of histological changes. The amount of malondialdehyde (MDA) in the colon was determined, along with the activity of myeloperoxidase (MPO), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Mucosa from the small intestine was collected to determine the levels of tumor necrosis factor (TNF)-α and interferon (IFN)-γ. The mucosa was ultrastructurally examined with transmission electron microscopy and intestinal permeability was assayed using Evans blue.
Results: Balsalazine was found to reduce the DAI score and the histological index (HI) score, decrease the MDA content and the activity of MPO, and increase the activity of SOD and GSH-Px in colitis mice. At the same time, balsalazine ameliorated microvillus and tight junction structure, resulting in a decrease in the amount of Evans blue permeating into the intestinal wall and the levels of TNF-α and IFN-γ in colitis mice.
Conclusion: In colitis mice, the anti-colitis effect of balsalazine results in a decrease in intestinal mucosal permeability. The mechanism of this effect is partly associated with balsalazine's antioxidative and anti-inflammatory effects. 相似文献
992.
Okayama M Hayashi S Aoi Y Nishio H Kato S Takeuchi K 《Digestive diseases and sciences》2007,52(9):2095-2103
We examined the effect of cyclooxygenase (COX) inhibitors on dextran sulfate sodium (DSS)-induced ulcerative colitis in rats
and investigated the role of COX isozymes in the pathogenesis of this model. Experimental colitis was induced by treatment
with 2.5% DSS in drinking water for 6 days. Indomethacin (a nonselective COX inhibitor), SC-560 (a selective COX-1 inhibitor),
or celecoxib (a selective COX-2 inhibitor) was given PO twice daily for 6 days, during the first 3 or last 3 days of the experimental
period. Daily treatment with 2.5% DSS for 6 days caused damage to the colon, with a decrease in body weight gain and colon
length as well as an increase of myeloperoxidase (MPO) activity. All COX inhibitors given for 6 days significantly worsened
the severity of DSS-induced colonic damage with increased MPO activity. The aggravation was also observed by SC-560 given
for the first 3 days or by celecoxib given for the last 3 days. The expression of COX-2 mRNA in the colon was upregulated
on day 3 during DSS treatment, with significant increase of prostaglandin E2 PGE2 production. The PGE2 content on day 3 during DSS treatment was inhibited by both indomethacin and SC-560, but not by celecoxib; on day 6 it was
suppressed by both indomethacin and celecoxib, but not SC-560. These results suggest that endogenous prostaglandins (PGs)
afford protection against colonic ulceration, yet the COX isozyme responsible for the production of PGs differs depending
on the stage of ulceration; COX-1 in the early stage and COX-2 in the late stage. 相似文献
993.
Identifying the subproteome of kinetically stable proteins via diagonal 2D SDS/PAGE 总被引:1,自引:0,他引:1 下载免费PDF全文
Xia K Manning M Hesham H Lin Q Bystroff C Colón W 《Proceedings of the National Academy of Sciences of the United States of America》2007,104(44):17329-17334
Most proteins are in equilibrium with partially and globally unfolded conformations. In contrast, kinetically stable proteins (KSPs) are trapped by an energy barrier in a specific state, unable to transiently sample other conformations. Among many potential roles, it appears that kinetic stability (KS) is a feature used by nature to allow proteins to maintain activity under harsh conditions and to preserve the structure of proteins that are prone to misfolding. The biological and pathological significance of KS remains poorly understood because of the lack of simple experimental methods to identify this property and its infrequent occurrence in proteins. Based on our previous correlation between KS and a protein's resistance to the denaturing detergent SDS, we show here the application of a diagonal 2D (D2D) SDS/PAGE assay to identify KSPs in complex mixtures. We applied this method to the lysate of Escherichia coli and upon proteomics analysis have identified 50 nonredundant proteins that were SDS-resistant (i.e., kinetically stable). Structural and functional analyses of a subset (44) of these proteins with known 3D structure revealed some potential structural and functional biases toward and against KS. This simple D2D SDS/PAGE assay will allow the widespread investigation of KS, including the proteomics-level identification of KSPs in different systems, potentially leading to a better understanding of the biological and pathological significance of this intriguing property of proteins. 相似文献
994.
Opposing effects of the prebiotic, fructooligosaccharide, have been reported in experimental colitis. We compared the effects
of the prebiotic, fructooligosaccharide, alone and in synbiotic combination with Lactobacillus fermentum BR11, on the development of dextran sulfate sodium-induced colitis in rats. Rats consumed an 18 percent casein-based diet
or diet supplemented with 6 percent fructooligosaccharide or maltodextrin for 14 days. The synbiotic group was gavaged 1 ml
of L. fermentum BR11 (1 × 109 cfu/ml) twice daily. From Days 7 to 14, colitis was induced via 3 percent dextran sulfate sodium in drinking water. Disease activity was assessed daily, and at killing, gastrointestinal
organs were measured, weighed, and examined by quantitative histology, proliferating cell nuclear antigen immunohistochemistry,
and colonic myeloperoxidase activity. Administration of dextran sulfate sodium resulted in an increased colitic disease activity,
and an increased colon and cecum weight compared with normal controls. Colon and cecum weights were further increased in dextran
sulfate sodium+fructooligosaccharide (colon: 19 percent; cecum: 48 percent) and dextran sulfate sodium+fructooligosaccharide/L. fermentum BR11-treated rats (16 and 62 percent) compared with dextran sulfate sodium+vehicle-treatment. Dextran sulfate sodium+fructooligosaccharide-treated
rats displayed an 81 percent increase in colonic myeloperoxidase activity compared with dextran sulfate sodium-treated controls.
Histologic damage severity scores increased in dextran sulfate sodium+vehicle, dextran sulfate sodium+fructooligosaccharide,
and dextran sulfate sodium+fructooligosaccharide/L. fermentum BR11-treated rats compared with normal controls (P < 0.05). Crypt depth increased in all treatments compared with normal controls (P < 0.01). No protection from dextran sulfate sodium-colitis was accorded by fructooligosaccharide alone or in synbiotic combination
with L. fermentum BR11, whereas fructooligosaccharide actually increased some indicators of colonic injury. 相似文献
995.
Severe gastrointestinal erosion, ulcer, necrosis and strictures after an acute iron overdose are well described. However, gastric mucosal injury in patients receiving therapeutic iron has received only scant recognition despite its wide use. We report a case of iron medication-induced gastric mucosal injury in a 76-year-old male who presented with iron deficiency anemia and had been taking ferrous sulfate tablet for 4 years. Esophagogastroduodenoscopy (EGD) revealed a pale, villous appearing flat lesion along the lesser curvature of gastric body. Histopathologic examination of EGD biopsies of the flat lesion showed brown crystalline materials deposited in the lamina propria of gastric mucosa, which was accompanied with fibrosis, chronic inflammation, and foreign body reaction. The crystalline materials were covered and admixed with gastric epithelium. Prussian blue iron stain confirmed that the brown crystalline materials were iron. The iron and hemosiderin accumulation was also seen in cytoplasm of epithelial cells and lumen of fundic gastric glands. The recognition and reporting by pathologists of iron-induced changes in EGD biopsies will alert clinicians to this underrecognized but easily correctable complication by alternative forms of iron therapy, such as liquid preparation. 相似文献
996.
遗传性多发性骨软骨瘤(hereditary multiple exotosis,HME)是一种常染色体显性遗传病,与EXT1和EXT2基因突变导致软骨生长异常有关.目前新突变位点的发现和相关研究进一步揭示了其遗传规律和特点.同时,分子学研究初步解释了其致病机制,提出了EXT基因突变导致硫酸肝素合成减少,最终影响软骨细胞信号转导过程而致病的假说.此外,多项临床研究初步分析了表型-基因型的联系,为更完整的了解HME及指导临床实践提供了新的观点和思路. 相似文献
997.
James Wang Brian OReilly Ramesh Venkataraman Vincent Mysliwiec Angela Mysliwiec 《Sleep medicine》2009,10(9):973-975
Background and PurposeRestless Legs Syndrome (RLS) is a primary disorder of sensation that affects sleep and has been associated with iron deficiency. The purpose of this study was to determine if symptomatic RLS patients with low-normal serum ferritin levels benefit from oral iron replacement.Patients and MethodsThis was a randomized, placebo-controlled, double-blinded study. Eligible patients were randomized to oral iron therapy vs. appearance-matched placebo and followed over a 12 week period.ResultsBaseline International Restless Leg Scale (IRLS) scores for the treatment (24.8 ± 5.72) and placebo (23.0 ± 5.03) groups were similar. Baseline ferritin levels for the treatment (40.6 ± 15.3 ng/ml) and placebo (36.7 ± 20.8 ng/ml) groups were also similar. After 12 weeks, IRLS scores decreased more in the treatment arm (10.3 ± 7.40) than in the placebo arm (1.14 ± 5.64), (p = 0.01). Ferritin levels increased more in the treatment arm (25.1 ± 20.3 ng/ml) than in the placebo arm (7.5 ± 13.7 ng/ml), (p = 0.04). We observed a nonsignificant trend toward improved quality of life in the treated patients, (p = 0.07).ConclusionsThis is the first double-blinded, placebo-controlled study to demonstrate statistically significant improvement in RLS symptoms using oral iron therapy in patients with low-normal ferritin. The findings from this study suggest that additional larger randomized placebo-controlled trials of iron as treatment for patients with low-normal ferritin are warranted. 相似文献
998.
目的:考察pH值和加入不同浓度金属离子络合物乙二胺四乙酸二钠(EDTA-Na2)对50%硫酸镁溶液中过氧化氢稳定性的影响,为过氧化氢作为防腐剂使用提供试验依据。方法:在pH值3.69、3.80、4.02、4.77、6.40、6.81和加入EDTA-Na20.01%、0.02%、0.04%、0.08%、0.16%的条件下,测定2厂家50%硫酸镁溶液中过氧化氢在贮存60d过程中的含量变化,分析pH值和EDTA-Na2对过氧化氢稳定性的影响。结果:不同pH值条件下过氧化氢贮存5d后含量均为0;加入0.04%以下浓度的EDTA-Na2贮存60d后过氧化氢含量均为0,加入0.04%以上浓度的EDTA-Na2贮存60d后过氧化氢的含量均约为50%。结论:溶液pH值对过氧化氢无稳定作用,加入EDTA-Na2对过氧化氢有一定的稳定作用。 相似文献
999.
微生物检定法测定庆大霉素普鲁卡因胶囊中庆大霉素含量的不确定度分析 总被引:1,自引:0,他引:1
目的:分析采用微生物检定法测定庆大霉素普鲁卡因胶囊中庆大霉素含量的不确定度以提高测定结果的准确性和可靠性。方法:根据《测量不确定度评定与表示》(JJF1059-1999)等中的有关规定,对该方法测定中各影响因素包括抑菌圈直径、抑菌圈测量仪、试验设计、标准品和供试品(称量、平均装量、纯度、稀释)等进行考察。确定主要影响因素及汇总得到扩展不确定度等。结果:量化了各分量的相对标准不确定度,并计算出总合成标准不确定度,得出扩展不确定度为2.98%;庆大霉素的含量为(88.41±2.98)%。主要影响因素为试验设计、抑菌圈直径和供试品平均装量等。结论:通过分析各分量的相对标准不确定度的大小来优化实验,严格规范操作,可使测定结果更加可靠。 相似文献
1000.