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61.
Ravikanth Bhamidipati P Venkatesh Prajakta V Dravid Prasad C Narasimhulu Sastry Tvrs Jagattaran Das Ramesh Mullangi Nuggehally R Srinivas 《European journal of drug metabolism and pharmacokinetics》2005,30(3):187-193
The aim of this study was to determine the bioavailability of a novel oxazolidinone, DRF-6196, in mice and rats following intravenous (i.v) and oral dosing and to compare the pharmacokinetics with those obtained following linezolid dosing. Blood samples were drawn at predetermined intervals up to 24 h post-dose after either DRF-6196 or linezolid administration. The concentrations of DRF-6196 and linezolid in various plasma samples were determined by a HPLC method. Following oral administration maximum concentrations of DRF-6196 were achieved within 0.5 h irrespective of the species. While the doses increased in the ratio of 1 : 3 : 10, mean Cmax and AUC(0-infinity) values in mice for DRF-6196 increased in the ratio of 1 : 3.87 : 8.53 and 1 : 2.51 : 9.24, respectively. Both the Cmax and AUC(0-infinity) values increased almost proportional to the dose administered in mice. Following i.v administration, the concentration of DRF-6196 declined in a bi-exponential fashion with terminal elimination half-life of 1.5 h irrespective of the species. The systemic clearance and volume of distribution of DRF-6196 in mice were 1.14 L/h/kg and 0.66 L/kg, respectively after i.v administration, while the respective values in rats were 0.61 L/h/kg and 0.41L/kg, respectively. Elimination half-life ranged between 0.8-1.5 h. Absolute oral bioavailability of DRF-6196 was found to be 80-96% across the test dose range. Although plasma levels of DRF-6196 were lesser compared to linezolid in the initial hours, it may not have any consequences on the clinical effectiveness of the molecule. 相似文献
62.
Mace L Rothenberg Bonnie LaFleur Donna E Levy Mary Kay Washington Sherry L Morgan-Meadows Ramesh K Ramanathan Jordan D Berlin Al B Benson Robert J Coffey 《Journal of clinical oncology》2005,23(36):9265-9274
PURPOSE: The clinical objective of this trial was to evaluate gefitinib in patients with metastatic colorectal cancer that had progressed despite prior treatment. Serial tumor biopsies were performed when possible and analyzed for activation of the epidermal growth factor receptor (EGFR) signaling pathway. Serial serum samples were measured for amphiregulin and transforming growth factor-alpha (TGFalpha). PATIENTS AND METHODS: One hundred fifteen patients were randomly assigned to receive gefitinib 250 or 500 mg orally once a day. One hundred ten patients were assessable for clinical efficacy. Biologic evaluation was performed on paired tumor samples from 28 patients and correlated with clinical outcome. RESULTS: Median progression-free survival was 1.9 months (95% CI, 1.8 to 2.1 months) and 4-month progression-free survival rate was 13% +/- 5%. One patient achieved a radiographic partial response (RR = 1%; 95% CI, 0.01% to 5%). Median survival was 6.3 months (95% CI, 5.1 to 8.2 months). The most common adverse events were skin rash, diarrhea, and fatigue. In the biopsy cohort, expression of total or activated EGFR, activated Akt, activated MAP-kinase, or Ki67 did not decrease following 1 week of gefitinib. However, a trend toward decreased post-treatment levels of activated Akt and Ki67 was observed in patients with a PFS higher than the median, although these did not reach the .05 level of significance. CONCLUSION: Gefitinib is inactive as a single agent in patients with previously treated colorectal cancer. In tumor samples, gefitinib did not inhibit activation of its proximal target, EGFR. Trends were observed for inhibition of downstream regulators of cellular survival and proliferation in patients achieving longer progression-free survival. 相似文献
63.
Manthena V.S. Varma Ramesh Panchagnula 《European journal of pharmaceutical sciences》2005,25(4-5):445-453
Solubility and permeability being important determinants of oral drug absorption, this study was aimed to investigate the effect of d--tocopheryl polyethylene glycol 1000 succinate (TPGS) on the solubility and intestinal permeability of paclitaxel in vitro, in situ and in vivo, in order to estimate the absorption enhancement ability of TPGS. Aqueous solubility of paclitaxel is significantly enhanced by TPGS, where a linear increase was demonstrated above a TPGS concentration of 0.1 mg/ml. Paclitaxel demonstrated asymmetric transport across rat ileum with significantly greater (26-fold) basolateral-to-apical (B–A) permeability than that in apical-to-basolateral (A–B) direction. Presence of P-glycoprotein (P-gp) inhibitor, verapamil (200 μM), diminished asymmetric transport of paclitaxel suggesting the role of P-gp-mediated efflux. TPGS showed a concentration-dependent increase in A–B permeability and decreased B–A permeability. The maximum efflux inhibition activity was found at a minimum TPGS concentration of 0.1 mg/ml, however, further increase in TPGS concentration resulted in decreased A–B permeability with no change in B–A permeability. Thus, the maximum paclitaxel permeability attained with 0.1 mg/ml TPGS was attributed to the interplay between TPGS concentration dependent P-gp inhibition activity and miceller formation. In situ permeability studies in rats also demonstrated the role of efflux in limiting permeability of paclitaxel and inhibitory efficiency of TPGS. The plasma concentration of [14C]paclitaxel following oral administration (25 mg/kg) was significantly increased by coadministration of TPGS at a dose of 50 mg/kg in rats. Bioavailability is enhanced about 4.2- and 6.3-fold when [14C]paclitaxel was administrated with verapamil (25 mg/kg) and TPGS, respectively, as compared to [14C]paclitaxel administered alone. The effect of verapamil on oral bioavailability of [14C]paclitaxel was limited relative to the TPGS, consistent with the in vitro solubility and permeability enhancement ability of TPGS. In conclusion, the current data suggests that the coadministration of TPGS may improve the bioavailability of BCS class II–IV drugs with low solubility and/or less permeable as a result of significant P-gp-mediated efflux. 相似文献
64.
Safety & efficacy of single subconjunctival triamcinolone 5 mg depot vs topical loteprednol post cataract surgery: less drop cataract surgery
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Jagadeesh Kumar Reddy Vivek Chaitany Neeraj Shah Venkata Prabhakar Guduru Shadab Khan Siddharthan Kuttupalayam 《国际眼科》2019,12(5):774-778
AIM: To do a randomized prospective interventional study for comparing the effects of a single subconjunctival triamcinolone acetonide (SCTA) injection to tapering topical loteprednol in patients undergoing phacoemulsification surgery under topical anesthesia.
METHODS: A total of 400 patients were randomized into 2 groups; Group A (200 patients) received 5 mg SCTA at the end of surgery and topical ketorolac tromethamine (0.5%) with ofloxacin (0.3%) combination for 3wk. Group B (200 patients) received tapering topical loteprednol etabonate (0.5%) along with ofloxacin (0.3%) and ketorolac tromethamine (0.5%) for 3wk. Outcomes evaluated were intraocular pressure (IOP), anterior chamber cells/flare and macular oedema postoperatively at 1, 6 and 12wk.
RESULTS: Baseline parameters were almost similar in both the groups. No statistical difference was seen between the preoperative and postoperative IOP values for Group A (P=0.82) and Group B (P=0.61) and postoperative IOP values in between both groups (P=0.14) at 1wk. Incidence of cells/flare postoperative was statistically not significant (P=0.82) in both groups at all follow up visits. Postoperative macular oedema was not observed at any follow up visit.
CONCLUSION: SCTA appears to be an effective alternative to prolong postoperative topical steroid use. 相似文献
65.
Kawasaki disease and giant coronary artery aneurysms: the role of echocardiography from diagnosis through follow‐up
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Adam C. Adler M.D. M.S. Ramesh Kodavatiganti M.D. 《Echocardiography (Mount Kisco, N.Y.)》2016,33(8):1245-1250
Kawasaki disease is an acquired vasculitis that can affect the coronary arteries placing the patient at risk for coronary artery thrombosis, myocardial ischemia and infarction. The risk of complications related to coronary artery involvement persists for years despite recovery from the acute illness phase. The risk of late coronary disease progression necessitates long term follow‐up generally accomplished by non‐invasive echocardiography in pediatric patients. We review the utility of echocardiography in patients with Kawasaki disease as it relates to initial management, risk stratification and follow‐up of these children. 相似文献
66.
67.
Endoscopic ultrasonography is not required for staging malignant esophageal strictures that preclude the passage of a diagnostic gastroscope
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68.
69.
Ramesh Kumar Sharma 《Indian Journal of Plastic Surgery》2013,46(2):167-Aug;46(2):167
70.
Pappu Ramesh Jabbour Serge A. Reginato Anthony M. Reginato Antonio J. 《Clinical rheumatology》2017,36(3):735-735
Clinical Rheumatology - 相似文献