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61.
62.
Diagnostic and predictive performance and standardized threshold of traditional biomarkers for drug‐induced liver injury in rats
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Yutaka Tonomura Yuki Kato Hiroyuki Hanafusa Yuji Morikawa Keigo Matsuyama Takeki Uehara Motonobu Ueno Mikinori Torii 《Journal of applied toxicology : JAT》2015,35(2):165-172
Traditional biomarkers such as alanine and aspartate aminotransferase (ALT, AST) and total bilirubin (TBIL) have been widely used for detecting drug‐induced liver injury (DILI). Although the Food and Drug Administration (FDA) proposed standardized thresholds for human as Hy's law, those for animals have not been determined, and predictability of these biomarkers for future onset of hepatic lesions remains unclear. In this study, we investigated these diagnostic and predictive performance of 10 traditional biomarkers for liver injury by receiver‐operating characteristic (ROC) curve, using a free‐access database where 142 hepatotoxic or non‐hepatotoxic compounds were administrated to male rats (n = 5253). Standardization of each biomarker value was achieved by calculating the ratio to control mean value, and the thresholds were determined under the condition of permitting 5% false positive. Of these 10 biomarkers, AST showed the best diagnostic performance. Furthermore, ALT and TBIL also showed high performance under the situation of hepatocellular necrosis and bile duct injury, respectively. Additionally, the availability of the diagnostic thresholds in difference testing facility was confirmed by the application of these thresholds to in‐house prepared dataset. Meanwhile, incorrect diagnosis by the thresholds was also observed. Regarding prediction, all 10 biomarkers showed insufficient performance for future onset of hepatic lesions. In conclusion, the standardized diagnostic thresholds enable consistent evaluation of traditional biomarkers among different facilities, whereas it was suggested that novel biomarker is required for more accurate diagnosis and prediction of DILI. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
63.
Baku Oyama Kei Morikawa Tadashi Sakaguchi Akihito Tsunoda Hirotaka Kida Takeo Inoue Masamichi Mineshita 《Internal medicine (Tokyo, Japan)》2021,60(3):441
An 83-years-old woman diagnosed with advanced Epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma was administered afatinib as a first-line treatment. On Day 17, the patient presented with grade 3 diarrhea and a blood test analysis showed an increased inflammatory response. Afatinib treatment was discontinued on the same day. On Day 26, the patient displayed blepharedema and multiple irregular erythema covering her entire body. Drug-induced hypersensitivity syndrome (DIHS) was suspected, and the systemic administration of 30 mg/day prednisolone was administered. The symptoms subsided thereafter. A blood test analysis 3 weeks after onset revealed a reactivation of Human herpesvirus 6 (HHV-6) and a diagnosis of DIHS due to afatinib therapy was confirmed. 相似文献
64.
Age-related collagen and elastin content of human heart valves 总被引:7,自引:0,他引:7
65.
Shinichi Nakamura Nobuyuki Torii Satoru Yatsuji Hiroyuki Konishi Maiko Kishino Makiko Taniai Katsutoshi Tokushige Etsuko Hashimoto Keiko Shiratori 《Hepatology research》2008,38(4):340-347
Aim: Because the procedure of balloon-occluded retrograde transvenous obliteration (B-RTO) causes extensive thrombosis of the major shunt that connects the spleen and gastric/renal venous systems, an increase in portal pressure is unavoidable. The aim of the present study was to assess the long-term outcome of B-RTO, including changes in esophageal varices. Methods: B-RTO was conducted in 22 patients with gastric varices, who were divided according to the severity of esophageal varices at baseline; there were no esophageal varices (n = 7), F(1) varices (n = 11), and F(2) varices (n = 4). The outcome measures included the development/worsening of esophageal varices after B-RTO and survival rates. Results: The cumulative bleeding-free probability for all 22 patients at 3 years after B-RTO was 100%. The overall 3-year survival was 94.4%. Seven patients who had no esophageal varices prior to B-RTO did not develop any after the procedure. Seven (63.6%) of the 11 patients with stage F(1) esophageal varices prior to B-RTO showed no changes in the varices after B-RTO, while two patients progressed to F(2) varices and two developed F(3) varices. The cumulative treatment-free probability of the esophageal varices at 24 months after B-RTO was 100% for patients without esophageal varices at baseline, 80.8% for patients with pre-existing F(1) varices, and 75% for those with pre-existing F(2) varices. Conclusion: Although the B-RTO procedure is considered useful for the treatment of gastric varices, changes in hemodynamics due to obliteration of this major shunt must be taken into account and observed closely. 相似文献
66.
The optimal combination of arterial grafts for quadruple coronary artery bypass is the bilateral internal mammary artery, the radial artery, and the gastroepiploic artery. Patients who underwent quadruple bypass in our hospital group between December 1995 and March 2001 were retrospectively analyzed to determine whether off-pump surgery (n = 27) provides better outcomes than conventional on-pump surgery (n = 51). Preoperative risk factors as well as the mean number of distal anastomoses (4.5 in the off-pump versus 4.8 in the on-pump patients) were not significantly different between the 2 groups. Postoperative recovery was significantly faster in the off-pump group than in the on-pump group (intubation time, 6.4 versus 16 hours; stay in intensive care unit, 2 versus 3 days; and postoperative hospital stay, 12.3 versus 15.8 days). Early stenosis-free graft patency rates did not differ significantly (90.3% versus 89.3%). No late cardiac events were observed in the off-pump group, while 4 occurred in the on-pump group. Quadruple arterial bypass without cardiopulmonary bypass is safe, and it allows faster recovery. The follow-up results of off-pump patients so far have been satisfactory. 相似文献
67.
Yasuji Arase M.D. Hiromitsu Kumada Kazuaki Chayama Akihito Tsubota Kenji Ikeda Satoshi Saitoh Yoko Sakai Toyomi Matsumoto Mariko Kobayashi 《Journal of gastroenterology》1992,27(5):646-651
Interferon (IFN) has been shown to be effective for chronic hepatitis C. This study investigated changes of alanine aminotransferase
(ALT) and HCV-RNA in chronic hepatitis C patients treated withα-IFN. IFN was given to 73 patients with HCV-RNA positive chronic hepatitis C. The pattern of changes in ALT activity after
IFN aministration was classified into five types. Type 1 was characterized by normalization of ALT (≤25 K.U) during IFN administration
and sustained normalization after the IFN therapy. Type 2 involved a rebound of ALT after termination of IFN therapy and subsequent
normalization. Type 3 had no ALT normalization during IFN administration, with normalization after the completion of the therapy.
Type 4 involved transient normalization of ALT level during IFN therapy, with a subsequent reversion to abnormal levels after
the termination of IFN therapy. Type 5 showed sustained abnormally high levels of ALT activity both during and after treatment.
Twenty four patients (32.9%) had sustained normalization ALT (≤25 K.U) after the termination of IFN treatment. The HCV-RNA
negative rate at 6 months after IFN therapy in patients with sustained normalization of ALT was 87.5% (21/24). 相似文献
68.
R353Q polymorphism, activated factor VII, and risk of premature myocardial infarction in Japanese men. 总被引:1,自引:0,他引:1
Masakazu Ogawa Satoshi Abe Sadatoshi Biro Masahiko Saigo Takashi Kihara Shiro Setoyama Tatsuru Matsuoka Hitoshi Toda Hiroyuki Torii Yoshihiko Atsuchi Yoshifumi Toyama Shigeki Tateishi Shinichi Minagoe Ikuro Maruyama Chuwa Tei 《Circulation journal》2004,68(6):520-525
BACKGROUND: The association between myocardial infarction (MI) and the R353Q polymorphism of the Factor VII (FVII) gene, which reportedly influences FVII concentrations, activated Factor VII (FVIIa), or FVII antigen (FVIIag), remains controversial. METHODS AND RESULTS: The present case - control study in 127 Japanese men with their first MI at or before 45 years of age and 150 matched healthy controls was designed to clarify this association in premature MI. R353Q polymorphism was determined by polymerase chain reaction, and plasma concentrations of FVIIa and FVIIag were assayed. The distribution of the RR, RQ, and QQ genotypes with respect to R353Q polymorphism was 117, 10, and 0 in the patients, and 131, 17, and 2 in the controls. The Q allele was negatively associated with premature MI (odds ratio =0.41, p=0.038). The plasma concentration of FVIIa was slightly higher in patients (55.1+/-40.9 U/L) than in controls (44.8+/-20.2 U/L), but not significantly (p=0.078); the plasma concentration of FVIIag did not differ between patients (88.7+/-15.7%) and controls (87.0+/-9.0%) (p=0.557). Plasma FVIIa concentrations were influenced by R353Q polymorphism (p<0.001). CONCLUSIONS: The Q allele may be protective against premature MI. 相似文献
69.
Skeletonized Radial Artery: New Technique for Graft Harvest with Improved Angiographic Results 总被引:1,自引:0,他引:1
Hitoshi?HiroseEmail author Atsushi?Amano Akihito?Takahashi 《The International journal of angiology》2003,12(4):252-256
To improve the patency rate of radial artery grafts, we have been using a skeletonized harvesting technique since September 2000. Our early reports confirmed better graft patency of skeletonized radial graft compared to conventional pedicled grafts. We present the angiographic and clinical follow-up data on skeletonized radial artery grafting. Between 09/01/2000 and 7/31/2002, a total of 268 patients underwent isolated coronary artery bypass using skeletonized radial artery graft, excluding T-grafting. Of these, 216 (80.6%) patients underwent postoperative angiography and their perioperative, early angiographic, and follow-up results were analyzed. There was 1 hospital death and 6 incidences of postoperative myocardial infarction. None were related to radial artery bypass. Early angiographic control revealed that the stenosis-free graft patency rate of radial artery anastomoses (318/331, 96.1%) was not significantly different from other conduits (the left internal mammary artery 93.5%, right internal mammary artery 90.8%, gastroepiploic artery 96.3%, and saphenous vein 97.6%). Follow-up was completed for all hospital survivors with a mean follow-up of 1.6 ± 0.4 years. There were no cardiac deaths, and 9 cardiac events, giving a cardiac event-free rate of 95.8%. The angiographical patency of the skeletonized radial artery was excellent. Although cardiac events were minimal, follow-up mid-term angiographics will be necessary to confirm our clinical outcome data. 相似文献
70.
Masayuki Tokuda Rie Miyamoto Tetsuya Sakuta Shigetaka Nagaoka Mitsuo Torii 《Connective tissue research》2013,54(3):153-158
Substance P (SP) induces the expression of proinflammatory cytokines, such as interleukin (IL)-6, which are implicated in pulp inflammation. To determine the signal pathway of SP-induced IL-6, we examined the activities of the mitogen-activated protein kinases (MAPKs) in human dental pulp cell (PF-10) cultures. SP induced the phosphorylation of p38 MAPK within 5 min; this activation persisted for up to 40 min and was independent of the activation of extracellular signal-related kinases (ERK-1 and ERK-2) that were induced after SP stimulation of PF-10 cells. As shown by electrophoretic mobility shift assay p38 MAPK was not involved in SP-induced activation of nuclear factor-kappa B (NF-κB). However, p38 MAPK mediated SP-induced IL-6 production, as shown by the use of specific inhibitors of this kinase. Our results suggest that the activation of p38 MAPK is important for NF-κB-independent regulator of neurogenic inflammation in dental pulp tissues. 相似文献