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111.
112.
Effects of HMGB1 on ischemia-reperfusion injury in the rat heart 总被引:1,自引:0,他引:1
Susumu Oozawa Shuji Mori Toru Kanke Hideo Takahashi Keyue Liu Yasuko Tomono Masato Asanuma Ikuko Miyazaki Masahiro Nishibori Shunji Sano 《Circulation journal》2008,72(7):1178-1184
BACKGROUND: Coronary ischemia-reperfusion (I/R) injury causes cardiomyocyte necrosis in a multi-step process that includes an inflammatory reaction. A recent study has suggested that high-mobility group box 1 (HMGB1) is a late mediator of lethal sepsis and an early mediator of inflammation and necrosis following I/R injury. In the present study a neutralizing monoclonal antibody (mAb) for HMGB1 was used to clarify the role of HMGB1 in cardiac I/R injury. METHODS AND RESULTS: Rats underwent 30 min of left coronary artery occlusion followed by 60 min reperfusion. An intravenous injection of anti-HMGB1 mAb or control IgG was administered just before reperfusion. The infarct size was enlarged in the anti-HMGB1 mAb group in comparison with the control group (p<0.05). The treatment of anti-HMGB1 mAb significantly increased the plasma troponin-T and norepinephrine (NE) content in the heart in comparison with the control (p<0.05). Moreover, the production of dihydroxyphenylglycol was reduced in the anti-HMGB1-treated group (p<0.05). CONCLUSION: This study shows for the first time the effects of treatment with neutralizing anti-HMGB1 mAb on I/R injury in the rat heart. The findings support the novel view that I/R-induced HMGB1 may be an important factor in the modulation of interstitial NE. 相似文献
113.
Noboru Fujino Masami Shimizu Hidekazu Ino Masato Yamaguchi Toshihiko Yasuda Mitsuru Nagata Tetsuo Konno Hiroshi Mabuchi 《The American journal of cardiology》2002,89(1):29-33
Familial hypertrophic cardiomyopathy (HC) can be caused by mutations in 9 different genes encoding sarcomere proteins expressed in cardiac muscle. To date, only 13 different mutations in the cardiac troponin T (cTnT) gene have been reported to cause HC. Clinical characteristics and prognosis associated with mutations of this gene have not been well characterized owing to the small size and composition of affected families. The aim of this study was to determine the characteristic phenotype of patients with HC caused by a novel cTnT gene mutation, Lys273Glu. Two hundred Japanese probands with HC were screened for mutations in the cTnT gene. The Lys273Glu missense mutation was present in 9 persons from 2 unrelated pedigrees. They exhibited different cardiac morphologies: 1 had a dilated cardiomyopathy-like feature, 7 had left ventricular hypertrophy with normal left ventricular systolic function, and the 6 of them had asymmetric septal hypertrophy. A 1-year-old boy was not evaluated with echocardiography. The mean maximum wall thickness was 18.0 +/- 5.5 mm (range 8 to 24). There were 7 histories of sudden death in 1 of the 2 families. The Lys273Glu substitution in the cTnT gene shows a high degree of penetrance (100% in persons aged >20 years), a high incidence of sudden death, and a partial transition from hypertrophic to dilated cardiomyopathy. Because the location of a mutation appears to influence the development of a phenotype, we suggest that the precise definition of the disease-causing mutation can provide important prognostic information about affected members. 相似文献
114.
115.
Takao Nishizawa Mitsunori Iwase Hiroaki Kanazawa Sahoko Ichihara Gaku Ichihara Kohzo Nagata Koji Obata Kiyoyuki Kitaichi Toyoharu Yokoi Masato Watanabe Takashi Tsunematsu Yoshihiro Ishikawa Toyoaki Murohara Mitsuhiro Yokota 《Circulation journal》2004,68(11):1051-1060
BACKGROUND: The relationship between enhanced myocardial oxidative stress and impaired beta-adrenergic signaling remains to be characterized during the development of dilated cardiomyopathy. METHODS AND RESULTS: Alterations in myocardial oxidative stress and beta-adrenergic signaling, as well as left ventricular (LV) functional and structural changes, were evaluated during the development of cardiomyopathy in TO-2 hamsters; F1B hamsters served as controls. LV dysfunction was first apparent at 8 weeks of age and deteriorated thereafter in the TO-2 hamsters. At 32 weeks, the animals exhibited heart failure with an increased plasma norepinephrine concentration. Cardiac myolysis, as demonstrated by elevated plasma concentration of cardiac troponin T, peaked at 8 weeks. The glutathione redox ratio revealed increased oxidative stress in the LV myocardium in TO-2 hamsters even at 4 weeks and became manifest after 8 weeks. The hearts of TO-2 hamsters had significantly reduced superoxide dismutase activity from 8 weeks onward compared with control hamsters. However, glutathione peroxidase activity was unchanged at any time point. The LV functional response to isoproterenol was markedly reduced at 8 weeks, without any apparent changes in the amount of beta-adrenergic signaling molecules, and it deteriorated thereafter. Adenylyl cyclase activity was significantly decreased, despite increased amounts of both G(s) alpha mRNA and protein, in the LV myocardium at 18 weeks. CONCLUSIONS: Myocardial oxidative stress is actually enhanced in the initial development of LV dysfunction. Both activation of myocardial oxidative stress and impairment of beta-adrenergic signaling become prominent at the stage of severe LV dysfunction. Myocardial oxidative stress may be involved in the development of beta-adrenergic desensitization. 相似文献
116.
Hiroyuki Kato Tatsushi Naganuma Yusuke Iizawa Masato Kitagawa Minoru Tanaka Shuji Isaji 《Journal of hepato-biliary-pancreatic sciences》2008,15(6):659-663
Primary lymphoma of the gallbladder is an exceedingly rare disease. We experienced an asymptomatic case of primary non-Hodgkin’s lymphoma of the gallbladder in a 55-year-old woman in whom laparoscopic cholecystectomy made a definite diagnosis. Abdominal computed tomography revealed a 4-cm gallbladder tumor with markedly enlarged lymph nodes in the retropancreatic area. Despite the marked involvement of lymph nodes, serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 were not elevated. The discrepancy between the imaging findings and the patient’s mild clinical presentation led us to suspect that the tumor was a lymphoma. We examined serum markers of lymphoma, revealing slight elevations of interleukin (IL)-2 receptor and thymidine kinase. Laparoscopic cholecystectomy for a total biopsy was performed successfully, and the results of intraoperative frozen-section examination led us to have a high suspicion of malignant lymphoma. The final diagnosis was large diffuse B-cell lymphoma of the gallbladder with a positive CD20 antibody reaction. The patient received postoperative chemotherapy with R-CHOP (rituximab, 500 mg; cyclophosphamide, 1000 mg; adriamycin, 68 mg; vincristine, 1.9 mg; and prednisone, 80 mg) starting on postoperative day 12. She achieved complete remission and is still in complete remission 3 years and 2 months after the cholecystectomy. In conclusion, gallbladder lymphoma should be added to the differential diagnosis of gallbladder tumors, especially when the imaging findings and clinical presentation are not consistent with typical signs of gallbladder carcinoma, and laparoscopic cholecystectomy is helpful for the confirmation of suspicious cases. 相似文献
117.
High plasma fibrinogen level is associated with poor clinical outcome in DIC patients 总被引:1,自引:0,他引:1
Wada H Mori Y Okabayashi K Gabazza EC Kushiya F Watanabe M Nishikawa M Shiku H Nobori T 《American journal of hematology》2003,72(1):1-7
We measured the plasma level of fibrinogen in 560 patients with disseminated intravascular coagulation (DIC) and evaluated its relationship with outcome and with other hemostatic markers. Forty-seven percent of patients had >200 mg/dL of plasma fibrinogen and 24% had <100 mg/dl of plasma fibrinogen, suggesting that plasma fibrinogen level is not a sensitive marker for DIC. In our analysis of outcome and plasma fibrinogen levels, the rate of death was high in leukemia/lymphoma patients with high fibrinogen concentration, but no significant difference in outcome was observed in relation to plasma fibrinogen concentration in non-leukemia/lymphoma patients with DIC. Among patients with leukemia/lymphoma, the frequency of organ failure was markedly high in patients with high plasma levels of fibrinogen. Among patients without leukemia/lymphoma, the frequency of organ failure increased concomitantly with the increase in plasma fibrinogen levels. The international normalized ratio was significantly increased in leukemia/lymphoma patients with low fibrinogen. FDP levels were slightly increased in patients with low fibrinogen. Platelet count was significantly low in patients without leukemia/lymphoma with high fibrinogen. DIC score increased concomitantly with the reduction in plasma fibrinogen levels. Plasma levels of thrombomodulin and tissue factor were significantly high in patients with high fibrinogen levels. Plasma levels of antiplasmin and plasminogen were significantly decreased in patients with low fibrinogen. Plasma levels of plasmin plasmin-inhibitor complex and tissue type plasminogen activator/plasminogen activator inhibitor-1 complex (PAI-I) were significantly higher in patients with low fibrinogen than in those with high fibrinogen. Plasma levels of PAI-I and IL-6 were significantly higher in patients with high fibrinogen than in those with low fibrinogen. Patients with high fibrinogen levels showed less activation of secondary fibrinolysis, which might explain the occurrence of organ failure and poor outcome. 相似文献
118.
Muneo Yoshibayashi MD Nagara Tamaki MD Kenya Nishioka MD Masahiko Matsumura MD Tadashi Ueda MD Shinji Temma MD Yoshiharu Yonekura MD Keiji Yamashita MD Junji Konishi MD Haruki Mikawa MD 《The American journal of cardiology》1991,68(17):1638-1645
To clarify the significance of newly appearing abnormal Q waves and their disappearance in patients with Kawasaki disease, regional myocardial perfusion and glucose metabolism at rest in the fasting condition were assessed by positron emission tomography (PET) with 13N-ammonia and 18F-fluorodeoxyglucose (FDG), and regional wall motion by left ventriculography in regions with persistent and transient abnormal Q waves in 14 patients. PET identified 3 groups of abnormal myocardial segments: segments with hypoperfusion without increased FDG uptake, those with hypoperfusion and increased FDG uptake, and those with normal perfusion and increased FDG uptake. Almost all the segments with persistent or transient abnormal Q waves had abnormal PET findings. PET demonstrated evidence of metabolic activity in 57% of segments with persistent abnormal Q waves and 67% of those with transient abnormal Q waves. Regional wall motion, scored from 0 (normal) to 4 (dyskinesia), was not significantly different between segments with persistent and transient abnormal Q waves (2.3 ± 1.3 vs 2.2 ± 1.2). The persistence of abnormal Q waves on serial electrocardiograms was significantly shorter in metabolically active than in inactive segments (19 ± 17 vs 92 ± 27 months). In conclusion, in patients with Kawasaki disease, the new appearance of abnormal Q waves is a reliable clue to the presence of ischemic myocardial injury and a high proportion of them are associated with metabolically active myocardial regions. The disappearance of abnormal Q waves does not necessarily mean the normalization of regional myocardial perfusion, metabolism or function, and their early disappearance may imply “viability” in the associated myocardial region. 相似文献
119.
Humic acid induces the endothelial nitric oxide synthase phosphorylation at Ser1177 and Thr495 Via Hsp90α and Hsp90β upregulation in human umbilical vein endothelial cells 下载免费PDF全文
Masato Tanaka Miki Miyajima Naoko Hishioka Ryo Nishimura Yusuke Kihara Toshiyuki Hosokawa Masaaki Kurasaki Shunitz Tanaka Takeshi Saito 《Environmental toxicology》2015,30(2):223-231
Humic acid (HA) has been implicated as a contributory factor for blackfoot disease, which is an endemic peripheral vascular disease. We investigated the effect of HA on the regulation of endothelial nitric oxide (NO) synthase (eNOS) in human umbilical vein endothelial cells (HUVECs) to evaluate the involvement of eNOS and related factors in peripheral vascular impairment with HA exposure. Treatment of HUVECs with HA induced upregulation of eNOS. This result coincides with those of previous studies. Furthermore this is the first study to report that HA induces upregulation of heat shock protein (Hsp)90α, Hsp90β, eNOS phosphorylation at Ser1177, and eNOS phosphorylation at Thr495, as compared to that in the control. In contrast, treatment with BAPTA, an intracellular Ca2+ chelator, inhibited upregulation of these proteins induced by HA. This study demonstrates that HA treatment leads to increases in both Hsp90α and Hsp90β proteins and indicates that Hsp90α leads to eNOS phosphorylation at Ser1177 and that Hsp90β leads to eNOS phosphorylation at Thr495, respectively. Upregulation of eNOS, Hsp90α, and Hsp90β in HUVECs is regulated by intracellular Ca2+ accumulation induced by HA. These results suggest that upregulation of eNOS phosphorylation at Ser1177 and eNOS phosphorylation at Thr495 produce NO and superoxide anions, respectively, resulting in generation of peroxynitrite, which causes impairment of vascular endothelial cells. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 223–231, 2015. 相似文献
120.
Flow cytometric examination of p53 protein in primary tumors and metastases to the liver and lymph nodes of colorectal cancer 总被引:2,自引:0,他引:2
Dr. Osamu Kimura M.D. Kenji Sugamura M.D. Tosihisa Kijima M.D. Masato Makino M.D. Hiroyuki Shirai M.D. Shigeru Tatebe M.D. Hisao Ito M.D. Nobuaki Kaibara M.D. 《Diseases of the colon and rectum》1996,39(12):1428-1433
PURPOSE AND METHODS: To confirm prognostic significance of overexpression of p53 in cases of colorectal cancer, expression of p53 protein was examined by flow cytometry in 113 cases of colorectal cancer and its metastasis to the liver and lymph nodes. RESULTS: Overexpression of p53 was found in 44 (39 percent) of the 113 primary tumors. There were no significant correlations among the level of p53 protein in the primary tumor, clinicopathologic features, and prognosis of colorectal cancer. Overexpression of p53 protein was detected in 72 percent (18/25) of liver metastases and in 40 percent (10/25) of lymph node métastases. Frequency of samples that were positive for p53 was significantly higher for liver metastases than for primary tumors and lymph node metastases (P<0.01). By comparing overexpression of p53 in primary tumors with that in corresponding secondary tumors, a decrease of more than 5 percent in the fluorescence index, compared with primary tumor, was not found in liver metastasis but was found in 20 percent of lymph node metastases. Incidence of cases with lower level expression of p53, compared with primary tumor, was significantly higher in lymph node metastases (32 percent) than in liver metastases (8 percent;P<0.05). CONCLUSIONS: From these results, it seems possible that overexpression of p53 may not be a good prognostic indicator of colorectal cancer and may be influenced by environments of the tumor.Presented at the meeting of the Japanese Gastroenterological Surgery, Fukui City, Japan, July 20 and 21, 1995. 相似文献