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61.
62.
Yashumati Ratan Bhardwaj Ashutosh Pareek Vivek Jain Dharma Kishore 《Saudi Pharmaceutical Journal》2014,22(4):290-302
Inclusion of metabolic considerations in the drug design process leads to significant development in the field of chemical drug targeting and the design of safer drugs during past few years which is a part of an approach now designated as Retro metabolic drug design (RMDD). This approach represents systematic methodologies that integrate structure–activity and structure–metabolism relationships and are aimed to design safe, locally active compounds with an improved therapeutic index. It embraces two distinct methods, chemical delivery systems and a soft drug approach. Present review recapitulates an impression of RMDD giving reflections on the chemical delivery system and the soft drug approach and provides a variety of examples to embody its concepts. Successful application of such design principles has already been applied to a number of marketed drugs like esmolol; loteprednol etc., and many other candidates like beta blockers, ACE inhibitors, alkylating agents, antimicrobials etc., are also under investigation. 相似文献
63.
Sriramoju Bharath Kumar Mettu Ravinder Golla Kishore Vaidya Jayathirtha Rao Perumal Yogeeswari Darmarajan Sriram 《Medicinal chemistry research》2014,23(4):1934-1940
Baylis–Hillman adduct-derived N-cinnamyl-substituted isatin derivatives were synthesized and evaluated for their antitubercular activity on Mycobacterium tuberculosis H37Rv strain ATCC 27294 by agar dilution method. Anticancer activity for the same compounds was also screened on four different cell lines: Chinese hamster ovary (CHO cells), Colo 205 (human colon cancer), Sup-T1 (human lymphoma) and C6 glioma (rat glioma) by MTT assay method. The compounds (3j–l) have shown significant activity against Mycobacterium strain and the compound 3l has shown specific cytotoxic activity. 相似文献
64.
Mamta Sachdeva Dhingra Pran Kishore Deb Renu Chadha Tejvir Singh Maninder Karan 《Medicinal chemistry research》2014,23(1):87-106
In our effort to identify the effective gastric sparing and protective anti-inflammatory agents, a series of cycloalkyl/aryl-3,4,5-trimethylgallates were synthesized and characterized. The physicochemical properties were studied to assess the lipophilicity and chemical stability. Subsequently, the compounds were evaluated for their anti-inflammatory activity and effect on gastric mucosa by most active compounds. All the compounds exhibited promising anti-inflammatory activity. In particular, 4a, 4b, 4g, and 4h emerged as the most active compounds in the series. The results of gastric mucosal studies and biochemical estimations suggested that these compounds are non-ulcerogenic and gastroprotective. The molecular docking analysis was performed to understand the binding interactions of these compounds to cyclooxygenase isoenzyme (COX-1 and COX-2). The results from this investigation suggests cycloalkyl/aryl-3,4,5-trimethylgallates as potent safer gastrosparing and protective anti-inflammatory agents. 相似文献
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66.
Effects of prior beta-blocker therapy on clinical outcomes after primary coronary angioplasty for acute myocardial infarction 总被引:9,自引:0,他引:9
Harjai KJ Stone GW Boura J Grines L Garcia E Brodie B Cox D O'Neill WW Grines C 《The American journal of cardiology》2003,91(6):655-660
We hypothesized that pretreatment with beta blockers may improve clinical outcomes after primary angioplasty for acute myocardial infarction. We pooled clinical, angiographic, and outcomes data on 2,537 patients enrolled in the Primary Angioplasty in Myocardial Infarction (PAMI), PAMI-2, and Stent PAMI trials. We classified patients into a beta group (n = 1,132) if they received beta-blocker therapy before primary angioplasty or a no-beta group (n = 1,405) if they did not. We evaluated procedural complications and in-hospital and 1-year outcomes (death and major adverse cardiac events [death, reinfarction, target vessel revascularization, or stroke]) between groups. Beta patients were younger, had higher systolic blood pressure and heart rate, and were more likely to be in Killip class I at admission. They had lower left ventricular ejection fraction, greater door-to-balloon time, greater likelihood of having a left anterior descending artery culprit lesion, but a similar incidence of Thrombolysis In Myocardial Infarction 3 flow after angioplasty (92.6% vs 92.7%, p = 0.91). The beta group had less procedural complications (23% vs 34%, p <0.0001) and a lower incidence of death (1.8% vs 3.7%, p = 0.0035) and major adverse cardiac events (5.5% vs 7.8%, p = 0.027) during hospitalization. At 1 year, mortality remained lower in beta patients (4.9% vs 6.7%, log-rank p = 0.055). After adjustment for baseline differences, beta patients had significantly lower in-hospital mortality (odds ratio 0.41; 95% confidence interval 0.20 to 0.84; p <0.0148) and nonsignificantly lower 1-year mortality (odds ratio 0.72; 95% confidence interval 0.47 to 1.08; p = 0.11). Thus, pretreatment with beta blockers has an independent beneficial effect on short-term clinical outcomes in patients undergoing primary angioplasty for acute myocardial infarction. 相似文献
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68.
Xin Zhou Yu-Hua Hui Loyd Hudson Kishore K. Katyayan Michael A. Mohutsky Junliang Hao Douglas A. Schober Erik J. Hembre 《Journal of pharmaceutical sciences》2019,108(2):1017-1026
1-Aminobenzotriazole (ABT) has been widely used as a nonspecific mechanism-based inhibitor of cytochrome P450 (P450) enzymes. It is extensively used in preclinical studies to determine the relative contribution of oxidative metabolism mediated by P450 in vitro and in vivo. The aim of present study was to understand the translation of fraction metabolized by P450 in dog hepatocytes to in vivo using ABT, for canagliflozin, known to be cleared by P450-mediated oxidation and UDP-glucuronosyltransferases–mediated glucuronidation, and 3 drug discovery project compounds mainly cleared by hepatic metabolism. In a dog hepatocyte, intrinsic clearance assay with and without preincubation of ABT, 3 Lilly compounds exhibited a wide range of fraction metabolized by P450. Subsequent metabolite profiling in dog hepatocytes demonstrated a combination of metabolism by P450 and UDP-glucuronosyltransferases. In vivo, dogs were pretreated with 50 mg/kg ABT or vehicle at 2 h before intravenous administration of canagliflozin and Lilly compounds. The areas under the concentration-time curve (AUC) were compared for the ABT-pretreated and vehicle-pretreated groups. The measured AUCABT/AUCveh ratios were correlated to fraction of metabolism by P450 in dog hepatocytes, suggesting that in vitro ABT inhibition in hepatocytes is useful to rank order compounds for in vivo fraction of metabolism assessment. 相似文献
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Danya Rosen Jaime Chu Rahul Patel Jang Moon Kishore Iyer Ronen Arnon 《Pediatric transplantation》2014,18(6):E193-E196
Gastric variceal bleeding is associated with high morbidity and mortality. Balloon‐occluded retrograde transvenous obliteration is a relatively new treatment used to control bleeding gastric varices that involves transvenous sclerosis of gastric varices through a spontaneous gastrorenal shunt. Here, we report on a 14‐yr‐old patient that underwent balloon‐occluded retrograde transvenous obliteration for refractory bleeding fundal varices in the setting of esophageal varices and cirrhosis, which did not respond to medical management or endoscopic injection. This case report serves as a reminder that balloon‐occluded retrograde transvenous obliteration can successfully control fundal variceal bleeding in pediatric patients and may serve as a bridge to liver transplantation. 相似文献