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41.
Deletions in the ligand for CD40 in X-linked immunoglobulin deficiency with normal or elevated IgM (HIGMX-1) 总被引:10,自引:0,他引:10
Ramesh Narayanaswamy; Fuleihan Ramsay; Ramesh Vijaya; Lederman Seth; Yellin Michael J.; Sharma Sunita; Chess Leonard; Rosen Fred S. 《International immunology》1993,5(7):769-773
Patients with X-linked Ig deficiency with normal or elevatedIgM (HIGMX-1) fail to switch from IgM/IgD to other Ig isotypes.Interaction between the B cell antigen CD40 and the CD40 ligandexpressed on activated T cells is critical for T cell drivenisotype switching. We have reported that T lymphocytes fromthree unrelated male patients with HIGMX-1 failed to expressCD40 ligand on their surface, but the mRNA for CD40 ligand wasof an apparently normal size and level. Analysis of CD40 ligandcDNA from two of the patients revealed deletions that alterthe reading frame. Patient 1 displayed two mutations: a C Atransversion at nucleotide 590 and the deletion of an adjacentC nucleotide. The second patient had a 58 bp deletion from nucleotides289–346. Furthermore, neither patient expressed a proteinproduct detectable by the CD40L mAb, 5c8. 相似文献
42.
Ravi Ramalingam K. K. Ramalingairr A. V. Ramesh S. Mahesh Prabhu Manu Vergis N. Ahilasamy 《Indian journal of otolaryngology and head and neck surgery》2003,55(4):294-295
The incidence of Papillary Thyroid Carcinoma in a Thyroglossal Cyst is rare. Only about 160 cases have been reported in the
last 85 years. We report a case of Thyroglossal Cyst who underwent Sistrunk ’s Operation. The Cyst was reported to
contain a focus of papillary thyroid carcinoma. In the absence of metastases in thyroid gland and neck nodes, only thyroid
suppression with Thyroxine was given. After I year of follow-up there are no metastases. The importance of Sistrunk’s
operation lies not only in complete removal of Thyroglossal Cyst but also in management of small foci of Papillary thyroid
Carcinoma. 相似文献
43.
The present study describes the formulation and evaluation for pharmacokinetic and pharmacodynamic activity of arginine vasopressin (AVP), a nanopeptide with antidiuretic activity on being delivered by transdermal iontophoresis. Poloxamer 407 was used to form stable gels that did not reduce the release of AVP. The release rate from the gel followed Higuchi kinetics indicating that the dominant mechanism of release is diffusion. Iontophoresis alone and in combination with chemical enhancers was used to augment the transdermal permeation of AVP. The results of both pharmacokinetic and pharmacodynamic studies emphasize the dimension of 'rapid onset' achieved by iontophoresis. The correlation between pharmacokinetic data and pharmacodynamic activity was only qualitative. Histopathological studies revealed that skin toxicity caused by either iontophoresis or chemical enhancers when used alone could be reduced by using a combination of both the techniques in tandem. 相似文献
44.
Effect of iontophoresis and fatty acids on permeation of Arginine Vasopressin through rat skin 总被引:9,自引:0,他引:9
The aim of this study was to assess the effects of fatty acids and iontophoretic mode of penetration enhancement on transdermal delivery of Arginine Vasopressin (AVP). Sprague-Dawley (SD) rat skin was pretreated with fatty acids (e.g. 5% w/v, lauric acid, oleic acid, and linoleic acid in ethanol:water (EtOH:W, 2:1 system) for 2h and iontophoresis in vitro, separately or together. The results indicate that all fatty acids studied increased (P<0.05) the flux of AVP in comparison to control (not pretreated with enhancer) and their effectiveness in flux enhancement was comparable. Further, oleic acid in combination with iontophoresis significantly increased the permeation of AVP both in comparison to pretreatment with fatty acids and iontophoresis alone. However, iontophoresis did not further increase the permeation of AVP through linoleic acid pretreated skin. Fourier transform infrared (FT-IR) spectroscopic studies revealed that EtOH:W (2:1) system is not effective in lipid extraction. The shift to higher wavenumbers of the symmetric and asymmetric stretching peaks at 2850 and 2920cm(-1) revealed that at the concentration used, oleic acid and linoleic acid caused fluidization of stratum corneum (SC) lipids. This study provides direct evidence that oleic acid in EtOH:W (2:1) system causes disruption of the SC lipid lamellae and that a combination of oleic acid with iontophoresis further enhances the effects of oleic acid in a synergistic manner. 相似文献
45.
Richard M Goldberg Daniel J Sargent Roscoe F Morton Charles S Fuchs Ramesh K Ramanathan Stephen K Williamson Brian P Findlay Henry C Pitot Steven R Alberts 《Journal of clinical oncology》2004,22(1):23-30
PURPOSE: Three agents with differing mechanisms of action are available for treatment of advanced colorectal cancer: fluorouracil, irinotecan, and oxaliplatin. In this study, we compared the activity and toxicity of three different two-drug combinations in patients with metastatic colorectal cancer who had not been treated previously for advanced disease. PATIENTS AND METHODS: Patients were concurrently randomly assigned to receive irinotecan and bolus fluorouracil plus leucovorin (IFL, control combination), oxaliplatin and infused fluorouracil plus leucovorin (FOLFOX), or irinotecan and oxaliplatin (IROX). The primary end point was time to progression, with secondary end points of response rate, survival time, and toxicity. RESULTS: A total of 795 patients were randomly assigned between May 1999 and April 2001. A median time to progression of 8.7 months, response rate of 45%, and median survival time of 19.5 months were observed for FOLFOX. These results were significantly superior to those observed for IFL for all end points (6.9 months, 31%, and 15.0 months, respectively) or for IROX (6.5 months, 35%, and 17.4 months, respectively) for time to progression and response. The FOLFOX regimen had significantly lower rates of severe nausea, vomiting, diarrhea, febrile neutropenia, and dehydration. Sensory neuropathy and neutropenia were more common with the regimens containing oxaliplatin. CONCLUSION: The FOLFOX regimen of oxaliplatin and infused fluorouracil plus leucovorin was active and comparatively safe. It should be considered as a standard therapy for patients with advanced colorectal cancer. 相似文献
46.
Prahlad Duggal S. Chakravorty Ramesh K. Azad Chander Mohan 《Indian journal of otolaryngology and head and neck surgery》2006,58(4):349-351
Dacryocystorhinostomy is performed in patients with naso-lacrimal duct obstruction to bypass the site of obstruction so as
to relieve the patient of the irritating and socially embarrassing symptoms of epiphora. We discuss the various epidemiological
aspects especially the vast difference by which the females out-number the males in patients undergoing DCR and the likely
explanations for this difference in our study on 74 patients which underwent DCR in our institute. 相似文献
47.
Yeragani VK Pohl R Jampala VC Balon R Ramesh C Srinivasan K 《Depression and anxiety》2000,11(3):126-130
This study investigated beat-to-beat QT variability in patients with panic disorder before and after treatment with nortriptyline (n = 13) and paroxetine (n = 16), using an automated algorithm to compute QT intervals. An increase in QT variability appears to be associated with symptomatic patients with dilated cardiomyopathy and also with an increased risk for sudden cardiac death. QTvi (QT variability index: a log ratio of QT variance normalized for mean QT over heart rate variability normalized for mean heart rate) was significantly higher in supine posture in patients with panic disorder treated with nortriptyline (P = 0.006) but not paroxetine. Thus paroxetine may be a better drug of choice especially in patients with coexisting cardiac disease. These findings are important especially in view of the recent reports of increased risk for cardiovascular mortality and sudden death in patients with anxiety and depression. QTvi can be a valuable noninvasive measure of temporal repolarization lability, especially to study the side effects of medications which affect cardiac autonomic function. 相似文献
48.
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
49.
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
50.
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