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991.
Yuya Matsue Makoto Suzuki Wataru Nagahori Kazuki Yoshida Yuko Onishi Yasuhiro Satoh Yuichi Ono Toshihiko Nishioka Makoto Noda Kaoru Sugi Sho Torii Tamotsu Tejima Harumizu Sakurada Satoshi Yamaguchi Kaoru Okishige Hiroyuki Fujii Atsushi Takahashi 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》2014,28(1):73-77
Purpose
Over half of all admitted acute decompensated heart failure (ADHF) patients have renal failure. Although diuretics represent the mainstay of treatment strategy even in this population, there are unmet needs for safer and more effective treatment. Tolvaptan is a vasopressin-2 receptor antagonist, and we hypothesized that adding tolvaptan to standard diuretic therapy would be more effective in ADHF patients with renal function impairment.Methods
The Answering question on tolvaptan’s efficacy for patients with acute decompensated heart failure and renal failure (AQUAMARINE) is a multicenter, randomized controlled clinical trial, which will enroll 220 patients from 17 hospitals in Japan. ADHF patients whose estimated glomerular filtration rate is above 15 and below 60 mL/min/1.72 m2 will be randomly assigned within 6 h after admission to usual care with furosemide or tolvaptan add-on therapy. Primary endpoint is achieved urine output within 48 h. Secondary endpoints include dyspnea relief measured by 7-points Likert scale, incidence of worsening renal function, dose of furosemide used within 48 h, and changes of brain natriuretic peptide.Conclusion
This study is the first multicenter study in Japan to evaluate clinical effectiveness of tolvaptan add-on therapy in ADHF patients with renal failure. The results of this study address the treatment strategy of this high-risk population (UMIN Clinical Trial Registry Number: UMIN000007109). 相似文献992.
Mai Ichikawa Tadashi Konoshita Takahiro Nakaya Katsushi Yamamoto Mika Yamada Satsuki Sato Michiko Imagawa Yasukazu Makino Miki Fujii Yasuo Zenimaru Kenichiro Arakawa Jinya Suzuki Tamotsu Ishizuka Hiroyuki Nakamura 《Acta diabetologica》2014,51(4):595-599
Recent genome-wide association studies have identified multiple variants that confer risk of type 2 diabetes mellitus (DM). However, established associations explain only a part of the heritability. Thus, even at the genome-wide association studies era, candidate gene approach should be still useful. Recent interventional studies against the renin-angiotensin system (RAS) showed reduction in new onset of DM, implying the system is involved in the onset. We substantiated the hypothesis that genetic variants of RAS have significant association with prevalence of DM. We enrolled to the study consecutive 782 subjects who had consulted our hospitals for mainly lifestyle related diseases. They consisted of 282 (36.1 %) diabetes cases. Genotypes were assayed with genomic DNA for conventional four genes of the RAS, i.e., angiotensin converting enzyme (ACE) insertion/deletion variant, angiotensinogen (AGT) M235T variant, angiotensin II type I receptor (AT1) A1166C variant, and aldosterone synthase (CYP11B2) C-344T variant. Association between the genetic variants of the RAS and prevalence of type 2 DM was tested. A significant association of DM and CYP11B2 genotype was obtained. There was no significant association between DM and ACE, AGT and AT1 variants. A multivariate logistic regression showed that age, gender, and CYP11B2 genotype were independent factors for association to diabetes, the DM risk of CC/CT to TT being 1.40 (95 % CI 1.04–1.90, p = 0.029). Thus, it is concluded that a genetic variant of the RAS should have a modest but significant impact on the onset of type 2 diabetes mellitus. 相似文献
993.
994.
Nobuharu Tamaki Masayuki Kurosaki Shuya Matsuda Masaru Muraoka Yutaka Yasui Shoko Suzuki Takanori Hosokawa Ken Ueda Kaoru Tsuchiya Hiroyuki Nakanishi Jun Itakura Yuka Takahashi Yasuhiro Asahina Namiki Izumi 《Journal of gastroenterology》2014,49(11):1495-1503
Background
The FIB-4 index is a simple formula to predict liver fibrosis. This study aimed to evaluate the utility of the FIB-4 index and associated time-course changes as a predictor of hepatocellular carcinoma (HCC) development.Methods
A total of 171 chronic hepatitis C patients who underwent paired liver biopsies and 875 patients who underwent a single liver biopsy (validation group) were investigated during mean follow-up periods of 6.4 and 5.9 years, respectively. All patients had received interferon therapy and had not achieved a sustained virological response. Factors associated with HCC development were analyzed in these patients.Results
HCC developed in 30 patients in the paired biopsy group and 89 patients in the validation group. Univariate analysis demonstrated that the FIB-4 index >3.25 and change in the FIB-4 index per year (ΔFIB-4/year) ≥0.3 were predictive factors for HCC development in both groups. Multivariate analysis in the combined population revealed that these two factors were independent. The hazard ratio (HR) for the FIB-4 index >3.25 was 2.7 (p < 0.001) and ΔFIB-4/year ≥0.3 was 1.8 (p = 0.003). Patients with a FIB-4 index >3.25 and a ΔFIB-4/year ≥0.3 were defined as high risk, and those with a FIB-4 index ≤3.25 and a ΔFIB-4/year <0.3 were defined as low risk. The HR of HCC development in patients at high risk was 7.3 (95 % confidence interval 4.3–12.5, p < 0.001).Conclusions
It was possible to define a group at high risk of developing HCC by intermittently measuring the FIB-4 index and considering time-course changes in this index. 相似文献995.
Terumi Kamisawa Kazuichi Okazaki Shigeyuki Kawa Tetsuhide Ito Kazuo Inui Hiroyuki Irie Takayoshi Nishino Kenji Notohara Isao Nishimori Shigeki Tanaka Toshimasa Nishiyama Koichi Suda Keiko Shiratori Masao Tanaka Tooru Shimosegawa 《Journal of gastroenterology》2014,49(6):961-970
The standard treatment for autoimmune pancreatitis (AIP) is steroid therapy, although some patients improve spontaneously. Indications for steroid therapy in AIP patients are symptoms such as obstructive jaundice, abdominal pain, back pain, and the presence of symptomatic extrapancreatic lesions. Prior to steroid therapy, obstructive jaundice should be managed by biliary drainage, and blood glucose levels should be controlled in patients with diabetes mellitus. The recommended initial oral prednisolone dose for induction of remission is 0.6 mg/kg/day, which is administered for 2–4 weeks. The dose is then tapered by 5 mg every 1–2 weeks, based on changes in clinical manifestations, biochemical blood tests (such as liver enzymes and IgG or IgG4 levels), and repeated imaging findings (US, CT, MRCP, ERCP, etc.). The dose is tapered to a maintenance dose (2.5–5 mg/day) over a period of 2–3 months. Cessation of steroid therapy should be based on the disease activity in each case. Termination of maintenance therapy should be planned within 3 years in cases with radiological and serological improvement. Re-administration or dose-up of steroid is effective for treating AIP relapse. Application of immunomodulatory drugs is considered for AIP patients who prove resistant to steroid therapy. The prognosis of AIP appears to be good over the short-term with steroid therapy. The long-term outcome is less clear, as there are many unknown factors, such as relapse, pancreatic exocrine or endocrine dysfunction, and associated malignancy. 相似文献
996.
Kazuichi Okazaki Shigeyuki Kawa Terumi Kamisawa Tetsuhide Ito Kazuo Inui Hiroyuki Irie Takayoshi Nishino Kenji Notohara Isao Nishimori Shigeki Tanaka Toshimasa Nishiyama Koichi Suda Keiko Shiratori Masao Tanaka Tooru Shimosegawa 《Journal of gastroenterology》2014,49(4):567-588
Background
In response to the proposal of the international consensus diagnostic criteria (ICDC) for autoimmune pancreatitis (AIP) and the Japanese diagnostic criteria in 2011, the 2009 Japanese consensus guidelines for managing AIP required revision.Methods
Three committees [the professional committee for making clinical questions (CQs) and statements by Japanese specialists, the expert panelist committee for rating statements by the modified Delphi method, and the evaluating committee by moderators] were organized. Fifteen specialists for AIP extracted the specific clinical statements from 1,843 articles published between 1963 and 2012 (obtained from Pub Med and a secondary database, and developed the CQs and statements. The expert panel individually rated the clinical statements using a modified Delphi approach, in which a clinical statement receiving a median score greater than seven on a nine-point scale from the panel was regarded as valid.Results
The professional committee created 13 CQs and statements for the current concept and diagnosis of AIP, 6 for extra-pancreatic lesions, 6 for differential diagnosis, and 11 for treatment.Conclusion
After evaluation by the moderators, amendments to the Japanese consensus guidelines for AIP have been proposed for 2013. 相似文献997.
Tsuyoshi Hamada Hideo Yasunaga Yousuke Nakai Hiroyuki Isayama Hiromasa Horiguchi Kiyohide Fushimi Kazuhiko Koike 《Journal of gastroenterology》2014,49(1):148-155
Background
Although several population-based studies have shown higher hospital volume (HV) to be associated with better outcomes in acute pancreatitis, they failed to adjust for disease severity and did not take into account the potentially non-linear relationship between HV and outcomes. Using a Japanese nationwide administrative database, this study aimed to evaluate the volume–outcome relationship in acute pancreatitis by means of statistical methods that permitted such considerations.Methods
In-hospital mortality, length of stay, and total costs for patients with acute pancreatitis were analyzed using multivariate regression models fitted with generalized estimating equations. Adjustment for severity was based on the Japanese Severity Scoring System and other patient characteristics. We used restricted cubic spline functions to examine the potential non-linear relationships between HV and outcomes.Results
In all, 17,415 eligible patients with acute pancreatitis were identified from 1,032 hospitals between 1 July 2010 and 30 September 2011. The in-hospital mortality rate was 2.6 %, and the median total costs were US $7,740 (interquartile range, 5,150–11,920). The overall and non-linear volume–outcome relationships were not significant either for in-hospital mortality or total costs. The median length of stay was 14 days (interquartile range, 10–22), and high HV was positively associated with shorter hospitalization (overall, P < 0.001; non-linear, P = 0.194).Conclusions
Despite the shorter hospitalization with higher HV, no inverse volume–outcome relationship was evident for acute pancreatitis. Further evidence is required to justify the volume-based selective referral of acute pancreatitis patients. 相似文献998.
Hiroyuki Murata Soichiro Ito Hiroyuki Kusuhara Yukihiro Nomura Toshio Taniguchi 《Journal of pharmaceutical sciences》2019,108(12):3898-3902
It is known that potent inhibition of organic-anion-transporting polypeptide (OATP)1B1 increases exposure to statins, leading to severe adverse effects. The aim of this study was to propose a parameter and its criteria in OATP1B1 inhibition assay at the early drug discovery stage to avoid compounds with the risk of statin-related adverse effects. According to drug label information, most compounds classified as “contraindicated” or “should be avoided” when administered concomitantly with statins increased their AUCs more than 4-fold. Generally, R values where R = 1 + plasma unbound fraction (fu) × maximum inhibitor concentration at the inlet to the liver/IC50 are used to evaluate the extent of clinical drug interaction. However, clinical doses and Cmax cannot be determined at the screening stage. Therefore, we estimated the correlations between change in AUC of statins concomitantly administered with OATP1B1 inhibitors and various parameters including fu/IC50. Cyclosporin A, rifampicin, and telaprevir increased the AUC of statins more than 4-fold and fu/IC50 of these compounds was >0.1 L/μmol. On the other hand, fu/IC50 of other compounds was ≤0.03 L/μmol. This study indicates that fu/IC50 is a useful parameter to avoid compounds that seriously affect statin potency through interaction with OATP1B1 at the screening stage. 相似文献
999.
1000.
Kobayashi Kentaro Manabe Osamu Hirata Kenji Yamaguchi Shigeru Kobayashi Hiroyuki Terasaka Shunsuke Toyonaga Takuya Furuya Sho Magota Keiichi Kuge Yuji Kudo Kohsuke Shiga Tohru Tamaki Nagara 《European journal of nuclear medicine and molecular imaging》2020,47(8):1833-1842
European Journal of Nuclear Medicine and Molecular Imaging - 18F-fluoromisonidazole (18F-FMISO) is the most widely used positron emission tomography (PET) tracer for imaging tumor hypoxia. Previous... 相似文献