全文获取类型
收费全文 | 5972篇 |
免费 | 276篇 |
国内免费 | 60篇 |
专业分类
耳鼻咽喉 | 53篇 |
儿科学 | 93篇 |
妇产科学 | 18篇 |
基础医学 | 761篇 |
口腔科学 | 155篇 |
临床医学 | 320篇 |
内科学 | 1592篇 |
皮肤病学 | 154篇 |
神经病学 | 281篇 |
特种医学 | 245篇 |
外科学 | 1010篇 |
综合类 | 30篇 |
预防医学 | 231篇 |
眼科学 | 83篇 |
药学 | 411篇 |
中国医学 | 36篇 |
肿瘤学 | 835篇 |
出版年
2023年 | 37篇 |
2022年 | 74篇 |
2021年 | 135篇 |
2020年 | 74篇 |
2019年 | 103篇 |
2018年 | 107篇 |
2017年 | 122篇 |
2016年 | 150篇 |
2015年 | 146篇 |
2014年 | 179篇 |
2013年 | 242篇 |
2012年 | 387篇 |
2011年 | 402篇 |
2010年 | 231篇 |
2009年 | 216篇 |
2008年 | 366篇 |
2007年 | 414篇 |
2006年 | 421篇 |
2005年 | 443篇 |
2004年 | 417篇 |
2003年 | 410篇 |
2002年 | 391篇 |
2001年 | 59篇 |
2000年 | 49篇 |
1999年 | 85篇 |
1998年 | 94篇 |
1997年 | 73篇 |
1996年 | 87篇 |
1995年 | 53篇 |
1994年 | 38篇 |
1993年 | 41篇 |
1992年 | 28篇 |
1991年 | 21篇 |
1990年 | 22篇 |
1989年 | 35篇 |
1988年 | 23篇 |
1987年 | 13篇 |
1986年 | 13篇 |
1985年 | 13篇 |
1984年 | 18篇 |
1983年 | 8篇 |
1982年 | 11篇 |
1981年 | 9篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1978年 | 5篇 |
1977年 | 4篇 |
1976年 | 6篇 |
1975年 | 7篇 |
1968年 | 3篇 |
排序方式: 共有6308条查询结果,搜索用时 15 毫秒
81.
Morinaga S Yamamoto Y Noguchi Y Imada T Rino Y Akaike M Sugimasa Y Takemiya S Takanashi Y 《Hepato-gastroenterology》2003,50(53):1521-1526
BACKGROUND/AIMS: Platelet-derived endothelial cell growth factor (PD-ECGF) is one of the angiogenic factors. The aim of this study was to examine the PD-ECGF concentrations in hepatocellular carcinoma, background liver, and normal liver tissues, and to elucidate their significance on clinicopathological outcomes. METHODOLOGY: The concentration of PD-ECGF in the tissue extract was determined by enzyme-linked immunosorbent assay. RESULTS: PD-ECGF concentrations were significantly higher in hepatocellular carcinoma and background liver tissues compared with normal control liver (p = 0.003, p = 0.001, respectively). PD-ECGF concentrations in hepatocellular carcinoma tissues were positively correlated with intratumoral arteriole densities (r = 0.667, p = 0.009), and were higher in less differentiated carcinomas (p = 0.039). However, tumor PD-ECGF concentration did not affect the patients' disease-free survival rates. Those in the background liver tissues were positively correlated with histological activity index scores (r = 0.650, p = 0.001) and serum alanine aminotransferase levels (r = 0.0452, p = 0.035). CONCLUSIONS: PD-ECGF is up-regulated in hepatocellular carcinoma and the corresponding hepatitis liver. The PD-ECGF concentrations in hepatocellular carcinoma correlated positively with microvessel density, lower differentiation, yet not with patients' prognosis. The concentrations of PD-ECGF in the corresponding hepatitis liver correlated positively with the degree of active hepatitis. 相似文献
82.
Fukuhara K Osugi H Takada N Takemura M Lee S Morimura K Taguchi S Kaneko M Tanaka Y Fujiwara Y Nishizawa S Fukushima S Kinoshita H 《Hepato-gastroenterology》2004,51(59):1515-1518
BACKGROUND/AIMS: Helicobacter pylori infection is known to induce gastritis, oxidative stress, and cyclooxygenase (COX)-2 expression in the gastric mucosa. However, the effect of H. pylori infection on remnant gastritis has not been studied. We investigated whether the severity of remnant gastritis and COX-2 expression were affected by H. pylori infection after distal gastrectomy. METHODOLOGY: The study included 97 patients with gastric cancer who underwent curative distal gastrectomy with lymphadenectomy in our department between May 1999 and April 2001. All patients underwent endoscopic examination 2 weeks before and 12 weeks after surgery. The presence of H. pylori infection was determined by urease activity, hematoxylin-eosin staining, and immunochemical staining. Histologic remnant gastritis was graded based on the degree of neutrophil infiltration using the updated Sydney System. COX-2 expression was estimated immunohistochemically. RESULTS: Both the degree of neutrophil infiltration and the level of COX-2 expression were significantly higher in patients with than without H. pylori (p<0.05). There was a significant correlation between the degree of neutrophil infiltration and the degree of COX-2 expression (p<0.001). CONCLUSIONS: H. pylori eradication may become a treatment for preventing both remnant gastritis as well as remnant gastric carcinoma after distal gastrectomy. 相似文献
83.
Up-regulation of transferrin receptor 1 in chronic hepatitis C: Implication in excess hepatic iron accumulation. 总被引:3,自引:0,他引:3
Hiroyuki Saito Yoshinori Fujimoto Takaaki Ohtake Yasuaki Suzuki Shinobu Sakurai Yayoi Hosoki Katsuya Ikuta Yoshihiro Torimoto Yutaka Kohgo 《Hepatology research》2005,31(4):203-210
BACKGROUND/AIMS:: To clarify the mechanism of excess hepatic iron accumulation in chronic hepatitis C, we investigated the expressions of transferrin receptor 1 and divalent metal transporter 1 in hepatocytes, both of which are involved in cellular iron uptake, in relation to the degree of hepatic iron accumulation and hepatic fibrosis by immunohistochemistrical study. METHODS:: Forty-six hepatic tissues with chronic hepatitis C and five normal hepatic tissues were examined. Chemical detection of hepatic iron accumulation was performed by Perl's Prussian blue stain. The immunohistochemistrical study was performed by avidin-biotin complex method with alkaline phosphatase. RESULTS:: In chronic hepatitis C: (1) Hepatic iron accumulation was significantly increased in relation to the advance of the fibrosis. (2) Divalent metal transporter 1 decreased significantly in relation to the advance of hepatic fibrosis. (3) Transferrin receptor 1 expression was always detected, although not in normal hepatic tissues; there was no relation between expression levels and the degree of hepatic fibrosis. CONCLUSIONS:: These data demonstrated that the transferrin receptor 1 expression was up-regulated irrespective of the degree of hepatic iron accumulation, suggesting that the up-regulation of transferrin receptor 1 might act as one of the key mechanisms implicated in the accumulation of hepatic iron in chronic hepatitis C. 相似文献
84.
Inhibitory effect of ceramide on insulin-induced protein kinase Czeta translocation in rat adipocytes 总被引:2,自引:0,他引:2
Miura A Kajita K Ishizawa M Kanoh Y Kawai Y Natsume Y Sakuma H Yamamoto Y Yasuda K Ishizuka T 《Metabolism: clinical and experimental》2003,52(1):19-24
Ceramide has been confirmed to be a signal mediator of apoptosis that is induced by tumor necrosis factor-alpha (TNF-alpha). It has also been reported that ceramide may induce insulin resistance as well as TNF-alpha. We investigated the effect of ceramide on insulin signaling pathways, such as insulin receptor (IR) beta-subunit, insulin receptor substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), and protein kinase Czeta (PKCzeta) in rat adipocytes. We examined insulin-stimulated [(3)H]2-deoxyglucose (2-DOG) uptake in rat adipocytes pretreated with N-hexanoylsphingosine (C(6)-ceramide, 10 to 30 micromol/L). Insulin-induced 2-DOG uptake was significantly reduced by C(6)-ceramide pretreatment. We also examined the effect of various concentrations of C(6)-ceramide pretreatment on insulin-induced autophosphorylation of the IR beta-subunit, tyrosine phosphorylation of IRS-1, enzyme activity of PI3K, and membrane-associated PKCzeta immunoreactivity. Pretreatment with C(6)-ceramide significantly reduced autophosphorylation of the IR beta-subunit, tyrosine phosphorylation of IRS-1, and enzyme activity of PI3K. Moreover, membrane-associated PKCzeta immunoreactivity and immunoprecipitable PKCzeta enzyme activity, downstream of PI3K, were significantly suppressed by C(6)-ceramide pretreatment. These results suggest that ceramide may induce insulin resistance via the suppression of IRS-1-PI3K signaling, and subsequent activation of PKCzeta. 相似文献
85.
Low-dose ethanol attenuates gut ischemia/reperfusion-induced liver injury in rats via nitric oxide production 总被引:2,自引:0,他引:2
Horie Y Yamagishi Y Kato S Kajihara M Kimura H Ishii H 《Journal of gastroenterology and hepatology》2003,18(2):211-217
BACKGROUND AND AIMS: The acute administration of low-dose ethanol was demonstrated to attenuate liver injury elicited by gut ischemia/reperfusion (I/R). Nitric oxide (NO) has been found to be a modulator of adhesive interactions between leukocytes, platelets, and endothelial cells, but there has been much controversy about the effects of ethanol on NO regulation. The objective of this study was to investigate the role of NO in ethanol-reduced hepatic microvascular dysfunction elicited by gut I/R. METHODS: Male Wistar rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Intravital microscopy was used to monitor leukocyte recruitment and non-perfused sinusoids (NPS). Plasma alanine aminotransferase (ALT) activities were measured 6 h after the onset of reperfusion. In another set of experiments, ethanol (10%, 1 g/kg) was administered before ischemia. RESULTS: Gut I/R elicited increases in the number of stationary leukocytes, NPS, and plasma ALT activities; all of which were attenuated by pretreatment with ethanol or an NO donor. Gut I/R caused the apoptosis of hepatocytes, which was prevented by pretreatment with ethanol. Pretreatment with an NO synthase inhibitor diminished the protective effects of ethanol. The administration of ethanol increased plasma nitrite/nitrate levels. CONCLUSION: These results suggest that low-dose ethanol attenuates the gut I/R-induced hepatic microvascular dysfunction and sequential liver injury by increasing sinusoidal NO levels. 相似文献
86.
A 51-year-old woman presented with flexion contractures of the legs. Physical examination showed decreased passive movements of the bilateral hip and knee joints without muscle spasms or neurological abnormalities. Laboratory evaluation showed no response of ACTH or plasma cortisol to stimulation with CRH or insulin. Diagnosis of isolated adrenocorticotropic hormone deficiency was made. The patient was started on prednisolone 5 mg daily, and flexion contractures of the legs rapidly disappeared. Although the musculoskeletal manifestation of this patient is similar to that of stiff-person syndrome, flexion contracture of the legs associated with adrenocortical insufficiency seems to be a separate disease entity from stiff-person syndrome. 相似文献
87.
Tanaka Y Matsui K Matsuda K Shinohara K Haranob K 《International journal of hematology》2005,82(2):124-126
A 48-year-old man had a 30-year history of hemolytic anemia of undetermined cause. Spherocytes were not observed, osmotic fragility was normal, and red cell enzyme activities were normal. His brother and daughter also had hemolytic anemia. The brother had previously undergone splenectomy, and the anemia had been ameliorated. In the proband and daughter, no abnormal hemoglobin was apparent in the results of isoelectric focusing and DEAE anion-exchange high-performance liquid chromatography analyses. On evaluation with the isopropanol test, unstable hemoglobin was not observed in the proband but was detected in the daughter. There was also a decreased ratio of 3 globin/3 globin chain production. Analysis of the 32 gene demonstrated the presence of a mutation (alpha43 [CE1] Phe --> Leu), hemoglobin Hirosaki. 相似文献
88.
Ikeda D Sakaue S Kamigaki M Ohira H Itoh N Ohtsuka Y Tsujino I Nishimura M 《Endocrinology》2008,149(12):6037-6042
Obesity is a condition in which adipose tissue mass is expanded. Increases in both adipocyte size and number contribute to enlargement of adipose tissue. The increase in cell number is thought to be caused by proliferation and differentiation of preadipocytes. Macrophage migration inhibitory factor (MIF) is expressed in adipocytes, and intracellular MIF content is increased during adipogenesis. Therefore, we hypothesized that MIF is associated with adipocyte biology during adipogenesis and focused on the influence of MIF on adipogenesis. To examine the effects of MIF on adipocytes, MIF expression in 3T3-L1 preadipocytes was inhibited by RNA interference, and cell differentiation was induced by standard procedures. The triglyceride content of MIF small interfering RNA (siRNA)-transfected 3T3-L1 cells was smaller than that of nonspecific siRNA-transfected cells. In addition, MIF knockdown apparently abrogated increases in adiponectin mRNA levels during differentiation. Gene expression of peroxisome proliferator-activated receptor (PPAR)gamma, CCAAT/enhancer binding protein (C/EBP)alpha, and C/EBPdelta decreased with MIF siRNA transfection, but C/EBPbeta expression increased. Cell number and incorporation of 5-bromo-2-deoxyuridine into cells decreased from 1-3 d and from 14-20 h, respectively, after induction of differentiation in MIF siRNA-transfected cells, thus suggesting that MIF siRNA inhibits mitotic clonal expansion. Taken together, these results indicated that MIF regulates differentiation of 3T3-L1 preadipocytes, at least partially, through inhibition of mitotic clonal expansion and/or C/EBPdelta expression. 相似文献
89.
OBJECTIVES: This study evaluated the significance of perfusion defects demonstrated by thallium-201 and age in the prognosis of patients with idiopathic dilated cardiomyopathy. METHODS: Seventy-four dilated cardiomyopathy patients underwent thallium scintigraphy as well as clinical and hemodynamic examination. RESULTS: Abnormal perfusion defects were present in 23 of 38 patients aged < 60 years (61%) and in 26 of 36 elderly patients aged > or = 60 years (72%; NS). Univariate analysis showed that such perfusion defects were a significant predictor of cardiac death only in patients aged < 60 years (p = 0.015). Stepwise discriminant analysis also revealed that perfusion defects were a significant predictor in patients aged < 60 years (Wilks' lambda 0.499, chi-square test 20.2, p = 0.003). Perfusion defects were not more important than the history of syncope or stroke in elderly dilated cardiomyopathy patients. Twenty-one patients died of disease-related causes during 58 +/- 43 months. The five-year survival rate was better in patients aged < 60 years without than in those with perfusion defects (100% vs 58.4%, respectively), but not affected in patients aged > or = 60 years (66.7% vs 62.2%). CONCLUSIONS: Thallium scintigraphy is valuable for the prognosis of patients with dilated cardiomyopathy aged < 60 years who are usually candidates for heart transplantation. Absence of thallium perfusion defects may indicate good long-term prognosis. 相似文献
90.
Telomerase activity and telomere length of peripheral blood mononuclear cells in SLE patients 总被引:4,自引:0,他引:4
Kurosaka D Yasuda J Yoshida K Yokoyama T Ozawa Y Obayashi Y Kingetsu I Saito S Yamada A 《Lupus》2003,12(8):591-599
We evaluated the clinical significance of the telomerase activity and telomere length of peripheral blood mononuclear cells (PBMC) in systemic lupus erythematosus (SLE). PBMC were isolated from 55 patients with SLE and the telomerase activity was measured by TRAP assay. The telomere length of PBMC was also measured in 30 of these subjects. As a control group, 45 healthy adults with no particular clinical history were studied. The results were compared with clinical data. In patients with active SLE, the telomerase activity of PBMC was significantly increased compared with the control group. In patients with inactive SLE, the PBMC telomerase activity was not different compared with the controls in their 20s, 30s and 40s, but it was significantly increased compared with the controls in their 50s. In SLE patients, the telomerase activity of PBMC was significantly correlated with modified SLEDAI. The telomere length of PBMC in younger SLE patients tended to be shorter than that in the controls, but no difference was observed in older patients. The correlation coefficient between the telomerase activity and telomere length of PBMC in SLE patients was not significant. Abnormalities in the telomerase activity and telomere length observed in SLE patients are considered to be important findings for evaluation of the pathology of SLE. 相似文献