全文获取类型
收费全文 | 27319篇 |
免费 | 2259篇 |
国内免费 | 1332篇 |
专业分类
耳鼻咽喉 | 87篇 |
儿科学 | 289篇 |
妇产科学 | 279篇 |
基础医学 | 4568篇 |
口腔科学 | 312篇 |
临床医学 | 1571篇 |
内科学 | 4799篇 |
皮肤病学 | 461篇 |
神经病学 | 2619篇 |
特种医学 | 379篇 |
外国民族医学 | 10篇 |
外科学 | 1592篇 |
综合类 | 3300篇 |
现状与发展 | 10篇 |
预防医学 | 545篇 |
眼科学 | 323篇 |
药学 | 4863篇 |
5篇 | |
中国医学 | 836篇 |
肿瘤学 | 4062篇 |
出版年
2024年 | 46篇 |
2023年 | 374篇 |
2022年 | 723篇 |
2021年 | 972篇 |
2020年 | 828篇 |
2019年 | 776篇 |
2018年 | 795篇 |
2017年 | 871篇 |
2016年 | 918篇 |
2015年 | 1088篇 |
2014年 | 1694篇 |
2013年 | 2079篇 |
2012年 | 1634篇 |
2011年 | 1978篇 |
2010年 | 1578篇 |
2009年 | 1618篇 |
2008年 | 1630篇 |
2007年 | 1508篇 |
2006年 | 1388篇 |
2005年 | 1192篇 |
2004年 | 1066篇 |
2003年 | 924篇 |
2002年 | 743篇 |
2001年 | 540篇 |
2000年 | 499篇 |
1999年 | 386篇 |
1998年 | 410篇 |
1997年 | 379篇 |
1996年 | 287篇 |
1995年 | 260篇 |
1994年 | 226篇 |
1993年 | 204篇 |
1992年 | 143篇 |
1991年 | 134篇 |
1990年 | 117篇 |
1989年 | 111篇 |
1988年 | 101篇 |
1987年 | 59篇 |
1986年 | 64篇 |
1985年 | 118篇 |
1984年 | 90篇 |
1983年 | 58篇 |
1982年 | 72篇 |
1981年 | 59篇 |
1980年 | 52篇 |
1979年 | 25篇 |
1978年 | 17篇 |
1977年 | 23篇 |
1976年 | 22篇 |
1975年 | 15篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Melatonin protects neurons from singlet oxygen-induced apoptosis 总被引:2,自引:2,他引:2
Cinzia M. Cagnoli Cagla Atabay Elena Kharlamova Hari Manev 《Journal of pineal research》1995,18(4):222-226
Abstract: Singlet oxygen (O2 [1 Δg]) is a very reactive molecule that can be produced by living cells and may contribute to cytotoxicity. The pineal hormone melatonin has been reported to possess potent antioxidant activity, and to be capable of scavenging O2 (1 Δg). We investigated whether melatonin might reduce the neurotoxic action of O2 (l Δg). The cytotoxic effect of singlet oxygen was studied in primary cultures of cerebellar granule neurons pretreated with a photosensitive dye, rose bengal, and exposed to light—a procedure that generates O2 (1 Δg). We found that this procedure triggers neuronal death, which is preceded by mitochondrial impairment (assayed by the rate of the reduction of MTT, 3-[4,5-di-methylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide, into formazan), and by DNA fragmentation—a marker of apoptosis. DNA fragmentation was determined in situ by terminal deoxynucleotidyl transferase assay; cell death was assayed with 0.4% trypan blue solution—viable cells with an intact membrane are not permeable to trypan blue; dead cells are, and thus, they are stained blue. Neuroprotection was obtained with the pineal hormone melatonin. In a cell-free system, melatonin also protected the enzyme creatine kinase (EC 2.7.3.2) from the rose bengal-induced injury. The results suggest that melatonin might counteract the cytotoxic action of singlet oxygen. Further studies are needed to clarify the exact role singlet oxygen and melatonin might play in neurodegenerative diseases. 相似文献
992.
Dina El-Dahshan Doaa Bahy Ahmed Wahid Amr E. Ahmed Amro Hanora 《Arab Journal Of Gastroenterology》2018,19(3):106-115
Background and study aims
The double-stranded RNA dependent protein kinase (PKR) plays a vital role in the immune system. During HCV infection, PKR has antiviral effect by inhibition of protein synthesis of the HCV. The functional single nucleotide polymorphisms (SNPs) in PKR promoter region might have a relation to HCV disease outcome and response to treatment. The objective of the present work was threefold. First, it proposed an optimized protocol for PCR amplification of PKR promoter. Second, it screened the promoter region of PKR gene in HCV Egyptian patients to detect the possible SNPs’ function. Third, to study the association between the detected SNPs and the response to treatment.Patients and methods
The functional SNPs in PKR promoter region were detected using DNA sequencing in 40 HCV infected patients; 20 sustained virologic response (SVR) patients and 20 nonresponse (NR) patients after combined interferon/ribavirin therapy. Twenty healthy subjects were included as a control.Results
Two functional SNPs were detected: rs62133148T>G and rs12992188C>T within our target PKR promoter region. In rs62133148 polymorphism, there is a significant difference between patients and control subjects for TT and TG genotypes (p?<?0.0001). In addition, the G allele is more predominant in HCV patients. In rs12992188 polymorphism, the CC genotype is significantly different between patients and healthy control subjects (OR/95% CI: 0.033/0.006–0.172, p?<?0.0001). The presence of C allele was significantly associated with the NR patients (OR/95%CI: 0.25/0.097–0.643, p?=?0.006). The TT genotype is significantly different between SVR and NR (OR/95%CI: 8.5/1.54–46.871, p?=?0.014).Conclusion
This study is a pioneer clinical study on these two functional SNPs (rs62133148T>G and rs12992188 C>T). The rs62133148 polymorphism does not show any association with response to treatment. The TT genotype in rs12992188 polymorphism shows association with response to treatment. Therefore, patients with TT genotypes were more likely to achieve SVR. 相似文献993.
994.
Intramyocardial synthesis of pro- and anti-inflammatory cytokines in infants with congenital cardiac defects 总被引:3,自引:0,他引:3
Qing M Schumacher K Heise R Wöltje M Vazquez-Jimenez JF Richter T Arranda-Carrero M Hess J von Bernuth G Seghaye MC 《Journal of the American College of Cardiology》2003,41(12):2266-2274
OBJECTIVES: We sought to test the hypothesis that cytokines would be expressed in the myocardium of infants with congenital cardiac defects and to identify the signaling pathways involved. BACKGROUND: Mechanical stress upregulates pro-inflammatory cytokines in the myocardium. METHODS: Fifteen infants with tetralogy of Fallot (TOF) (n = 7) or with ventricular septal defects (VSDs) (n = 8) were investigated. Concentrations of pro- and anti-inflammatory cytokines and of the inducible nitric oxide synthase (iNOS) were measured by enzyme-linked immunosorbent assay and/or Western blotting in the right ventricular myocardium taken during cardiac surgery. Activation of the nuclear factor-kappa-B (NF-kappa-B) and p38 mitogen-activated protein kinase (MAPK) pathways was assessed by electrophoretic mobility shift assay with supershift and/or Western blotting, respectively. RESULTS: The pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1-beta, and IL-6 and the anti-inflammatory cytokine IL-10 were detected in the myocardium of all patients. Concentrations of the pro-inflammatory cytokines and also of phosphorylated p38 MAPK were higher in patients with TOF than in those with VSD and correlated with the degree of pressure overload of the right ventricle. Levels of phosphorylated I-kappa-B-alpha, iNOS, and IL-10 were similar in patients with TOF and in those with VSD. CONCLUSIONS: Our results show intramyocardial synthesis of pro-inflammatory cytokines in infants with congenital cardiac defects. This is associated with activation of both the NF-kappa-B and p38 MAPK pathways. The latter could be particularly important for the transduction of mechanical signals in the infant's myocardium. Synthesis of IL-10 indicates an intramyocardial anti-inflammatory potential in this age group. 相似文献
995.
Tumor necrosis factor-induced protection of the murine heart is independent of p38-MAPK activation 总被引:5,自引:0,他引:5
Tanno M Gorog DA Bellahcene M Cao X Quinlan RA Marber MS 《Journal of molecular and cellular cardiology》2003,35(12):1523-1527
Brief exposure to tumor necrosis factor (TNF) is known to trigger subsequent cardioprotection. TNF activates multiple downstream signaling cascades including p38-MAPK, a kinase known to initiate ischemic preconditioning. However, it is not known whether this kinase is similarly involved in TNF-induced cardioprotection. In isolated perfused murine hearts, subjected to 30-min global ischemia/2-h reperfusion, infarction/risk volume was significantly reduced by pretreatment with TNF for 15 min at 0.5 ng/ml, but not at 5 or 10 ng/ml, followed by 10-min washout vs. control (% I/R = 31 +/- 3, 46 +/- 5 or 54 +/- 3 vs. 48 +/- 5; P = 0.01, 0.80 and 0.25, respectively). This was in direct contrast to the concentration dependence of myocardial p38-MAPK phosphorylation, as measured by dual phosphorylated p38-MAPK, which was apparent at TNF concentrations of 5 and 10 ng/ml but not at 0.5 ng/ml vs. time-matched control (as % basal 315 +/- 25, 422 +/- 94 and 97 +/- 25 vs. 95 +/- 10; P < 0.01, 0.01 and =0.86, respectively). However, phosphorylation of p38-MAPK at 10 min of ischemia was similar among groups (as % basal 393 +/- 98, 410 +/- 67 and 369 +/- 49 for time-matched control, 0.5 and 5 ng/ml, respectively). These patterns were also reflected in the phosphorylation of the downstream substrate HSP27. Furthermore, the effects of TNF on infarct size were not affected by SB203580 (1 micromol/l). These findings suggest that the pre-ischemic activation of p38-MAPK by TNF does not contribute to cardioprotection afforded by this agent. 相似文献
996.
Lovastatin controls signal transduction in vascular smooth muscle cells by modulating phosphorylation levels of mevalonate-independent pathways 总被引:1,自引:0,他引:1
Lovastatin has been proven to effectively lower circulating LDL cholesterol and to exert antiproliferative effects on various
cell lines, the latter effect being only incompletely understood. We found that lovastatin modulates the signal transducing
phosphorylation cascade in vascular smooth muscle cells in a mevalonate-independent manner. Lovastatin was found to distinctively
increase total phosphotyrosine levels in smooth muscle cells, an effect which could not be restored by mevalonate. At a concentration
of 5 μmol/L lovastatin had a highly specific effect on the mitogen-activated protein kinase pathway. The expression of p42/44
mitogen-activated protein kinase (MAPK) was clearly reduced, but could be restored by addition of mevalonate, while the phosphorylation
of p44 was mildly suppressed and the phosphorylation of p42 MAPK was reduced to non-detectable levels. While the phosphorylation
of p44 MAPK could partially be restored by addition of mevalonate, the reduced phosphorylation of p42 MAPK could not be restored
by addition of excessive doses of mevalonate or stimulation of the cells with basic fibroblast growth factor. Concurrently
the expression of the GTP-binding Ras protein was significantly elevated at 5 and 20 μmol/L lovastatin, this effect being
attenuated by addition of mevalonate to cell cultures.
The data indicate that lovastatin is capable of modulating cellular signaling independently of the cholesterol synthesis pathway.
Received: 30 August 2000, Returned for 1. revision: 20 September 2000, 1. Revision received: 14 November 2000, Returned for
2. revision: 28 November 2000, 2. Revision received: 11 December 2000, Accepted: 12 December 2000 相似文献
997.
998.
Wai CT Fontana RJ Polson J Hussain M Shakil AO Han SH Davern TJ Lee WM Lok AS;US Acute Liver Failure Study Group 《Journal of viral hepatitis》2005,12(2):192-198
The role of hepatitis B virus (HBV) genotypes in the outcome of acute HBV infection is unclear. In this study, we aimed to evaluate the clinical and virological features of patients with hepatitis B-related acute liver failure (HBV-ALF) in the US. Clinical and laboratory features of consecutive patients with HBV-ALF from the US ALF Study Group were analysed. Prevalence of HBV genotypes, precore stop (G1896A) and core promoter dual (T1762A, A1764T) variants among patients with HBV-ALF were compared with a cohort of 530 patients with chronic HBV infection. Thirty-four HBV-ALF patients were studied: mean age 41 years, 56% men, 25 had detectable HBV-DNA. HBV genotypes A, B, C and D were found in 36, 24, 8 and 32% patients, respectively. Precore stop and core promoter dual variants were detected in 32 and 44% of patients, respectively. Twenty-three (68%) patients survived: 14 after liver transplant, nine without transplant. Older age was the only independent factor associated with poor outcome. Compared with patients with chronic HBV infection, patients with ALF were more likely to be non-Asians (88% vs 44%, P = 0.005) and to have genotype D (32% vs 10%, P < 0.01). A higher prevalence of HBV genotype D persisted even after matching for race and HBeAg status (32% vs 16%, P = 0.007). We concluded that HBV genotype D was more frequently found in patients with HBV-ALF than those with chronic HBV infection in the US. Further studies are needed to determine if HBV genotypes play a role in the outcome of acute HBV infection. 相似文献
999.
Desrois M Sidell RJ Gauguier D Davey CL Radda GK Clarke K 《Journal of molecular and cellular cardiology》2004,37(2):547-555
Aging and diabetes in women increase their susceptibility to myocardial ischemic injury, but the cellular mechanisms involved are not understood. Consequently, we studied the influence of gender on cardiac insulin resistance and ischemic injury in the aging of Goto-Kakizaki (GK) rat, a model of type 2 diabetes. Male and female GK rats had heart/body weight ratios 29% (P < 0.0001) and 53% (P < 0.0001) higher, respectively, than their sex-matched controls, with the female GK rat hearts significantly more hypertrophied than the male (P < 0.001). Glucose transporter (GLUT) 1 protein levels were the same in all hearts, but GLUT4 protein levels were 28% lower (P < 0.01) in all GK rat hearts compared with their sex-matched controls. In isolated, perfused hearts, insulin-stimulated (3)H-glucose uptake rates were decreased by 23% (P < 0.05) and 40% (P < 0.05) in male and female GK rat hearts, respectively, compared with their controls, with the female significantly more insulin resistant than the male GK rat hearts (P < 0.05). Protein kinase B protein levels and insulin-stimulated phosphorylation were the same in all hearts. During low-flow ischemia, glucose uptake was 59% lower (P < 0.001) in female, but the same as controls in male, GK rat hearts. Consequently, recovery of contractile function during reperfusion was 30% lower (P < 0.05) in female, but the same as controls in male GK rat hearts. We conclude that the aging female type 2 diabetic rat heart has increased insulin resistance and greater susceptibility to ischemic injury, than non-diabetic or male type 2 diabetic rat hearts. 相似文献
1000.
Although it is generally accepted that tumour growth is angiogenesis dependent, little is known about the role of angiogenesis
in the metastatic process. Recent evidence suggests that the angiogenic tyrosine kinase receptor KDR is pivotal in new vessel
formation. To investigate, therefore, the association between new vessel formation in primary breast carcinoma and axillary
lymph node metastasis we have used computer assisted video analysis to assess the vascular distribution as well as the level
of expression of KDR in individual vessels in sections of invasive breast carcinomas, some of which had metastasized to the
axillary lymph nodes and some that had not. We specifically assessed the frequency distribution, perimeter, area, and density
of KDR positive vessels in the same sections of tumours. Our results show that in invasive mammary carcinoma KDR is expressed
exclusively on the surface and cytoplasm of endothelial cells of approximately 71% of vessels, but the level of expression
in individual vessels does not correlate with the presence of axillary lymph node metastases (P > 0.10). However, we found
that small vessels express higher levels of KDR (P < 0.02) than larger vessels and that there is a significantly higher frequency
of relatively small (< 90 μm in perimeter) KDR positive vessels in breast tumours that had metastasized to the axillary lymph
nodes than those that had not (P < 0.001). In conclusion, increased density and frequency of KDR positive small vessels in
primary invasive breast carcinoma correlates with axillary lymph node metastases.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献