全文获取类型
收费全文 | 412篇 |
免费 | 14篇 |
国内免费 | 20篇 |
专业分类
儿科学 | 5篇 |
基础医学 | 46篇 |
口腔科学 | 7篇 |
临床医学 | 18篇 |
内科学 | 82篇 |
皮肤病学 | 1篇 |
神经病学 | 46篇 |
特种医学 | 7篇 |
外科学 | 20篇 |
综合类 | 36篇 |
预防医学 | 11篇 |
眼科学 | 5篇 |
药学 | 144篇 |
中国医学 | 10篇 |
肿瘤学 | 8篇 |
出版年
2023年 | 1篇 |
2022年 | 3篇 |
2021年 | 9篇 |
2020年 | 8篇 |
2019年 | 22篇 |
2018年 | 18篇 |
2017年 | 7篇 |
2016年 | 9篇 |
2015年 | 22篇 |
2014年 | 25篇 |
2013年 | 36篇 |
2012年 | 21篇 |
2011年 | 35篇 |
2010年 | 31篇 |
2009年 | 29篇 |
2008年 | 24篇 |
2007年 | 18篇 |
2006年 | 17篇 |
2005年 | 18篇 |
2004年 | 16篇 |
2003年 | 17篇 |
2002年 | 8篇 |
2001年 | 3篇 |
2000年 | 11篇 |
1999年 | 6篇 |
1998年 | 6篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1995年 | 4篇 |
1994年 | 2篇 |
1989年 | 1篇 |
1985年 | 1篇 |
1984年 | 4篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1978年 | 1篇 |
1977年 | 1篇 |
排序方式: 共有446条查询结果,搜索用时 15 毫秒
1.
SB203580对肾缺血/再灌注损伤时细胞凋亡及p38MAPK影响的实验研究 总被引:9,自引:0,他引:9
目的 探讨不同时间及不同浓度p38MAPK特异性抑制剂SB2 0 35 80对肾缺血 /再灌注损伤过程中肾功能、细胞凋亡及 p38MAPK活性、表达量、p38MAPK底物的影响。 方法 4 9只大鼠按缺血 /再灌注及给药时间的不同 ,随机分为 7组 ,每组7只大鼠按正交拉丁方表的顺序 ,经尾静脉注射相同体积、不同剂量的SB ,使其在大鼠体内达到不同的浓度。测定BUN和Scr;用TUNEL试剂盒检测细胞凋亡情况 ;Westernblot技术用于蛋白定性及半定量分析。结果 SB可显著减轻大鼠肾缺血 /再灌注损伤造成的Scr和BUN的升高、肾小管上皮细胞的凋亡及 p38MAPK的激活 ,但存在模型、剂量及给药时机的差异 (P<0 .0 5 ) ,缺血前 3h之前给药 ,使其体内血药浓度达到 5 μmol/L左右可取得较好的效果。 结论 SB可显著减轻大鼠肾缺血 /再灌注损伤 ,在缺血前 3h之前给药 ,同时使其血药浓度达到 5 μmol/L左右可取得最佳效果。 相似文献
2.
IL-8 mRNA in human gingival epithelial cells (HGECs) is up-regulated by Fusobacterium nucleatum, and up-/down-regulated by Porphyromonas gingivalis in a complex interaction in the early stages (< or = 4 h) after infection. The mechanisms involved in this regulation in response to F. nucleatum and/or P. gingivalis infection, and identification of co-regulated cytokine genes, are the focus of this investigation. Heat, formalin or protease treatment of F. nucleatum cells attenuated the IL-8 mRNA up-regulation. NF-kappaB, mitogen-activated protein kinase (MAPK) p38 and MAPK kinase/extracellular signal-regulated kinase (MEK/ERK) pathways were involved in IL-8 mRNA induction by F. nucleatum. Pretreatment of P. gingivalis with heat, formalin or protease enhanced IL-8 mRNA induction. NF-kappaB, MARK p38, and MEK/ERK pathways were also involved in this induction. In contrast, down-regulation of IL-8 mRNA by P. gingivalis involved MEK/ERK, but not NF-kappaB or MAPK p38 pathways. cDNA arrays analysis revealed that mRNA down-regulation by P. gingivalis is a specific reaction that only a number of genes, e.g. IL-1beta, IL-8, macrophage inflammatory protein-2alpha, and migration inhibitory factor-related protein-14, are affected based on examination of 278 cytokine/receptor genes. These data indicate that F. nucleatum and P. gingivalis trigger specific and differential gene regulation pathways in HGECs. 相似文献
3.
Fedja A. Rochling 《Nutrients》2021,13(3)
The development of intestinal failure-associated liver disease (IFALD) in pediatric and adult patients on parenteral nutrition is usually multifactorial in nature due to nutritional and non-nutritional causes. The role of lipid therapy as a contributing cause is well-established with the pathophysiological pathways now better understood. The review focuses on risk factors for IFALD development, biological effects of lipids, lipid emulsions and the mechanisms of lipid toxicity observed in laboratory animals followed by a synopsis of clinical studies in pediatric and adult patients. The introduction of fish oil-based lipid emulsions that provide partial or complete lipid replacement therapy has resulted in resolution of IFALD that had been associated with soybean oil-based therapy. Based on case reports and cohort studies in pediatric and adult patients who were at risk or developed overt liver disease, we now have more evidence that an early switch to partial or complete fish oil–based lipid therapy should be implemented in order to successfully halt and reverse IFALD. 相似文献
4.
D. W. P. Hay Mark A. Luttmann Roseanna M. Muccitelli Roy G. Goldie 《Naunyn-Schmiedeberg's archives of pharmacology》1999,359(5):404-410
Tension and phosphatidyl inositol (PI) turnover experiments were conducted to investigate the receptors and signal transduction
pathways responsible for contractions elicited by endothelin (ET) ligands in human bronchus. Nicardipine (1 μM), the L-type
calcium channel inhibitor, or incubation in Ca2+-free medium, produced marked inhibition of contractions to the ETB receptor-selective agonist, sarafotoxin S6c, and especially those induced by KCl. In contrast, Ca2+-free medium was without appreciable effect against contraction produced by endothelin-1 (ET-1), the non-selective ETA and ETB receptor agonist. In Ca2+-free medium, ryanodine (10 μM), which inhibits intracellular calcium mobilization, reduced sarafotoxin S6c- and ET-1-induced
responses, but was without effect on responses to KCl. Similarly, nickel chloride (Ni2+; 1 mM) caused marked inhibition of contractions induced by sarafotoxin S6c or ET-1, but had no significant effect on KCl
concentration-response curves. The mixed ETA/ETB receptor antagonist SB 209670 (3 μM) inhibited responses to sarafotoxin S6c and ET-1 such that concentration-response curves
were shifted rightward, at the 30% maximum response level, by 10.0- and 3.8-fold, respectively, whereas BQ-123 (3 μM), the
ETA receptor antagonist, was without effect on responses induced by either agonist. ET-1 (1 nM–0.3 μM) caused a concentration-dependent
stimulation of PI turnover, whereas sarafotoxin S6c (0.3 nM–0.1 μM) induced only small and variable increases, except at the
highest concentration. The increase in PI turnover evoked by ET-1 was inhibited by SB 209670 (3 μM), and also by BQ-123 (3
μM). This is consistent with linkage of ETA receptors to activation of inositol phosphate generation in human bronchial smooth muscle cells. Collectively, the data suggest
that differences exist in the relative contributions of intracellular and extracellular Ca2+ mobilization mechanisms elicited by ETA and ETB receptor activation. Thus, sarafotoxin S6c-induced, ETB receptor-mediated contraction in human bronchial smooth muscle appears to be dependent, in part, upon extracellular Ca2+, although a significant component of the response was also mediated by intracellular Ca2+ release, including from ryanodine-sensitive stores. ETA receptor-mediated contraction of human airway smooth muscle was activated largely via the release of intracellular Ca2+.
Received: 21 July 1998 / Accepted: 26 January 1999 相似文献
5.
Zsolt Szabo Csongor Fabo Adam Oszlanyi Fatime Hawchar Tibor Gczi Judit Lantos Jozsef Furk 《Journal of thoracic disease》2022,14(8):3045
Background and ObjectiveThanks to the growing experience with the non-intubated anesthetic and surgical techniques, most pulmonary resections can now be performed by using minimally invasive techniques. The conventional method, i.e., surgery on the intubated, ventilated patient under general anesthesia with one-lung ventilation (OLV) was considered necessary for the major thoracoscopic lung resections for all patients. An adequate analgesic approach (regional or epidural anesthesia) allows video-assisted thoracoscopy (VATS) to be performed in anesthetized patients and thus the potential adverse effects related to general anesthesia and mechanical OLV can be minimized.MethodsMultiple medical literature databases (PubMed, Google Scholar, Scopus) were searched, using the terms [(non-intubated) OR (nonintubated) OR (tubeless) OR (awake)] AND [(thoracoscopic surgery)] from 2004 to December 2021. Thirty hundred and six scientific papers were collected. The editorials, commentaries, letters, and papers were excluded, that focus on other than the non-intubated (aka awake or tubeless) VATS technique, as well as the full text scientific papers available in languages other than English.Key Content and FindingsAfter reviewing the literature, we identified “schools” with different techniques but with very similar results. Most of the differences were in the anesthetic technique, oxygenation and analgesia, however, the immunological results, and the qualitative parameters (inpatient hospital care days, complication rate, mortality) of the perioperative period showed great similarity, in addition, all three schools identified the same risk factors (hypoxia, hypercapnia, airway safety). The combination of spontaneous ventilation with double lumen tube intubation, called VATS-spontaneous ventilation with intubation (SVI) method seems to be suitable for reducing these risk factors, which may serve as an alternative for patients not suitable for the non-intubated technique in the near future.ConclusionsBased on the results, non-intubated thoracic surgery appears to be an increasingly widespread, safe procedure, that will be available to a wider range of patients as experience expands and by the implication of the constantly evolving new processes. 相似文献
6.
促肝细胞生长素联合复方丹参注射液治疗慢性重型肝炎临床疗效观察 总被引:1,自引:0,他引:1
目的:探讨慢性重型肝炎的治疗方法,降低其病死率。方法:在综合治疗的基础上,采用促肝细胞生长素(HGF)联合复方丹参注射液治疗慢性重型肝炎。结果:HGF与丹参合用,能降低血清胆红素(SB),缩短凝血酶原时间(PT)复常时间,降低病死率,与对照组相比有显著性差异(P<0.01)。结论:慢性重型肝炎治疗的疗程较长,二者联合使用能有效缩短疗程,且二者的使用环节不同,可能有协同或相加作用。 相似文献
7.
Xiao-ke Ji Yuan-kang Xie Jun-qiao Zhong Qi-gang Xu Qi-qiang Zeng Yang Wang Qi-yu Zhang Yun-feng Shan 《Acta pharmacologica Sinica》2015,36(3):334-342
Aim:
Glycogen synthase kinase 3β (GSK-3β) plays a crucial role in hepatic biology, including liver development, regeneration, proliferation and carcinogenesis. In this study we investigated the role of GSK-3β in regulation of growth of hepatic oval cells in vitro and in liver regeneration in partially hepatectomized rats.Methods:
WB-F344 cells, the rat hepatic stem-like epithelial cells, were used as representative of oval cells. Cell viability was examined using a WST-8 assay. The cells were transfected with a recombinant lentivirus expressing siRNA against GSK-3β (GSK-3βRNAiLV) or a lentivirus that overexpressed GSK-3β (GC-GSK-3βLV). Adult rats underwent partial (70%) hepatectomy, and liver weight and femur length were measured at d 7 after the surgery. The expression of GSK-3β, phospho-Ser9-GSK-3β, β-catenin and cyclin D1 was examined with immunoblotting assays or immunohistochemistry.Results:
Treatment of WB-F344 cells with the GSK-3β inhibitor SB216763 (5 and 10 μmol/L) dose-dependently increased the levels of phospho-Ser9-GSK-3β, but not the levels of total GSK-3β, and promoted the cell proliferation. Knockout of GSK-3β with GSK-3βRNAiLV increased the cell proliferation, whereas overexpression of GSK-3β with GC-GSK-3βLV decreased the proliferation. Both SB216763 and GSK-3βRNAiLV significantly increased the levels of β-catenin and cyclin D1 in the cells, whereas GSK-3β overexpression decreased their levels. In rats with a partial hepatectomy, administration of SB216763 (2 mg/kg, ip) significantly increased the number of oval cells, the levels of phospho-Ser9-GSK-3β, β-catenin and cyclin D1 in liver, as well as the ratio of liver weight to femur length at d 7 after the surgery.Conclusion:
GSK-3β suppresses the proliferation of hepatic oval cells by modulating the Wnt/β-catenin signaling pathway. 相似文献8.
Xin-xin Xiong Ju-mei Liu Xin-yao Qiu Feng Pan Shang-bin Yu Xiao-qian Chen 《Acta pharmacologica Sinica》2015,36(3):362-374
Aim:
To investigate the effects of piperlongumine (PL), an anticancer alkaloid from long pepper plants, on the primary myeloid leukemia cells from patients and the mechanisms of action.Methods:
Human BM samples were obtained from 9 patients with acute or chronic myeloid leukemias and 2 patients with myelodysplastic syndrome (MDS). Bone marrow mononuclear cells (BMMNCs) were isolated and cultured. Cell viability was determined using MTT assay, and apoptosis was examined with PI staining or flow cytometry. ROS levels in the cells were determined using DCFH-DA staining and flow cytometry. Expression of apoptotic and autophagic signaling proteins was analyzed using Western blotting.Results:
PL inhibited the viability of BMMNCs from the patients with myeloid leukemias (with IC50 less than 20 μmol/L), but not that of BMMNCs from a patient with MDS. Furthermore, PL (10 and 20 μmol/L) induced apoptosis of BMMNCs from the patients with myeloid leukemias in a dose-dependent manner. PL markedly increased ROS levels in BMMNCs from the patients with myeloid leukemias, whereas pretreatment with the antioxidant N-acetyl-L-cysteine abolished PL-induced ROS accumulation and effectively reduced PL-induced cytotoxicity. Moreover, PL markedly increased the expression of the apoptotic proteins (Bax, Bcl-2 and caspase-3) and autophagic proteins (Beclin-1 and LC3B), and phosphorylation of p38 and JNK in BMMNCs from the patients with myeloid leukemias, whereas pretreatment with the specific p38 inhibitor SB203580 or the specific JNK inhibitor SP600125 partially reversed PL-induced ROS production, apoptotic/autophagic signaling activation and cytotoxicity.Conclusion:
Piperlongumine induces apoptotic and autophagic death of the primary myeloid leukemia cells from patients via activation of ROS-p38/JNK pathways. 相似文献9.
Tae-Min Rhee Kyung Woo Park Chi-Hoon Kim Jeehoon Kang Jung-Kyu Han Han-Mo Yang Hyun-Jae Kang Bon-Kwon Koo Hyo-Soo Kim 《JACC: Cardiovascular Interventions》2018,11(24):2453-2463
Objectives
The aim of this study was to investigate clinical outcomes after left main coronary artery (LM) bifurcation percutaneous coronary intervention (PCI) and the impact of the duration of dual antiplatelet therapy (DAPT) according to treatment strategy.Background
There are limited data regarding the optimal PCI strategy for LM bifurcation lesions with new-generation drug-eluting stents.Methods
A patient-level pooled analysis of 5 nationwide multicenter registries was performed. Rates of target lesion failure, thrombotic adverse cardiovascular events, and their individual components at 3-year were analyzed. Subgroup analysis according to DAPT duration was performed.Results
From 13,172 patients undergoing PCI with new-generation drug-eluting stents, a total of 700 patients were treated for LM bifurcation lesions, 567 with a 1-stent strategy and 133 with a 2-stent strategy. Rates of target lesion failure and target lesion revascularization were higher in the 2-stent group, driven mainly by complex lesion profiles. Risks for thrombotic adverse cardiovascular events and its components were comparable between the 2 strategies. Subgroup analysis showed that risks for target lesion failure and thrombotic adverse cardiovascular events in the 2-stent group were significantly higher than in the 1-stent group in those with DAPT interruption <1 year, while they were similar in those receiving DAPT maintenance ≥1 year.Conclusions
Up to 20% of patients who underwent LM bifurcation PCI eventually required a 2-stent strategy, which was as safe as a 1-stent strategy with the use of new-generation drug-eluting stents. Careful pre-emptive case selection as well as prolonged DAPT may be necessary when considering a 2-stent strategy in LM PCI given its higher rate of repeat revascularization and lesion failure than the 1-stent approach. 相似文献10.