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排序方式: 共有303条查询结果,搜索用时 46 毫秒
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Chhaya V Verma Rachna D Arora Hetal M Mistry Swati V Kubal Nandini S Kolwankar Pranali C Patil Anushka A Dalvi Sonal A Vichare Akhila Natesan Anagha N Mangaonkar Dolly D Kanakia Gayatri S Jere Karan Y Bansode Madhura R Patil Rajvi D Sheth Sandhya D Dudhavade Sayali D Mhatre Suresh K Patel Akanksha G Mohite Ankita N Bhavsar Jessica E Alfonso Maryam NA Syed Nidhi P Savla Riya N Rajgond Rutuja A Bute Samiksha M Mane Shubham R Jaiswal Vibhawari A Parab Abhiram M Kasbe Mohan A Joshi Ramesh N Bharmal 《Indian Journal of Critical Care Medicine》2021,25(3):317
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Peranandam Revathi Palanisamy Iyapparaj Lourduraj Arockia Vasanthi Natesan Munuswamy Muthukalingan Krishnan 《Environmental toxicology》2014,29(10):1171-1181
The present investigation documents the impact of tributyltin (TBT) on the ultrastructural variation of spermatogenesis in freshwater prawn Macrobrachium rosenbergii. The environmentally realistic concentration of TBT can cause damages to the endocrine and reproductive physiology of crustaceans. In this context, three concentrations viz. 10, 100, and 1000 ng/L were selected and exposed to prawns for 90 days. The TBT exposed prawn exhibited decrease the reproductive activity as evidenced by sperm count and sperm length compared to control. Histopathological results revealed the retarded testicular development, abnormal structure of seminiferous tubule, decrease in the concentration of spermatozoa, diminution of seminiferous tubule membrane, abundance of spermatocytes and vacuolation in testis of treated prawns. Ultrastructural study also confirmed the impairment of spermatogenesis in treated prawns. Furthermore, radioimmunoassay (RIA) clearly documented the reduction of testosterone level in TBT exposed groups. Thus, TBT substantially reduced the level of male sex hormone as well as biochemical constituents which ultimately led to impairment of spermatogenesis in the freshwater male prawn M.rosenbergii. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1171–1181, 2014. 相似文献
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S Natesan S Ashworth J Nielsen S-P Tang C Salinas S Kealey J B Lauridsen T B Stensb?l R N Gunn E A Rabiner S Kapur 《Translational psychiatry》2014,4(4):e376
A number of phosphodiesterase 10A (PDE10) inhibitors are about to undergo clinical evaluation for their efficacy in treating schizophrenia. As phosphodiesterases are in the same signalling pathway as dopamine D2 receptors, it is possible that prior antipsychotic treatment could influence these enzyme systems in patients. Chronic, in contrast to acute, antipsychotic treatment has been reported to increase brain PDE10A levels in rodents. The aim of this study was to confirm these findings in a manner that can be translated to human imaging studies to understand its consequences. Positron emission tomography (PET) scanning was used to evaluate PDE10A enzyme availability, after chronic haloperidol administration, using a specific PDE10A ligand ([11C]MP-10). The binding of [11C]MP-10 in the striatum and the cerebellum was measured in rodents and a simplified reference tissue model (SRTM) with cerebellum as the reference region was used to determine the binding potential (BPND). In rats treated chronically with haloperidol (2 mg kg−1 per day), there was no significant difference in PDE10A levels compared with the vehicle-treated group (BPND±s.d.: 3.57±0.64 versus 2.86±0.71). Following PET scans, ex vivo analysis of striatal brain tissue for PDE10A mRNA (Pde10a) and PDE10A enzyme activity showed no significant difference. Similarly, the PDE10A protein content determined by western blot analysis was similar between the two groups, contrary to an earlier finding. The results of the study indicate that prior exposure to antipsychotic medication in rodents does not alter PDE10A levels. 相似文献
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Melatonin is an important hormone regulating circadian clocks in birds, but the specific cellular sites of action are not completely known. The present study was designed to determine whether astrocytes derived from chick brain contained functional melatonin receptors. Primary cell cultures of diencephalon astrocytes that express glial fibrillary acidic protein (GFAP), but not neuron-specific enolase (NSE) immunoreactivity, were employed to determine the cellular distribution and physiological role for the three known receptor subtypes. Saturation and Scatchard analysis of 2-[(125)I]iodomelatonin binding demonstrated melatonin receptor binding with a high affinity and a pharmacological profile similar to that obtained from brain. In situ hybridization for receptor subtypes revealed Mel(1A) and Mel(1C) receptor mRNA, but not Mel(1B). Administration of pharmacological levels of melatonin acutely inhibited forskolin-stimulated 2-deoxyglucose (2DG) uptake, while rhythmic administration of physiological levels of melatonin gradually imposed a rhythm in 2DG uptake and of the release of both lactate and pyruvate into the medium. These results indicate that (1) there are functional Mel(1A) and Mel(1C) melatonin receptors in astrocyte-rich cultures, and (2) rhythmic administration of melatonin plays an important role in the regulation of astrocytic metabolic activity. Together, the data suggest that the circadian secretion of melatonin probably plays a role in the global metabolic economy of the avian brain through rhythmic regulation of metabolism in astrocytes. 相似文献
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The topical delivery of celecoxib has been studied using microemulsion as the vehicle for the treatment of UV B induced skin cancer. Pseudotemary phase diagrams were constructed at different oil to cosurfactant ratios to identify the formulation variables for microemulsion formation, and the effect of these variables on skin permeation of celecoxib was evaluated with excised rat skin. Topical anti-inflammatory effect of celecoxib has been assessed using the arachidonic acid induced ear oedema model. Formulation E consisting of 3% celecoxib, 22% propylene glycol dicaprylate/dicaprate + caprylic/capric mono-/di-glycerides (2:1), 30% polysorbate 80 and water (all w/w) showed higher permeation rate and significant anti-inflammatory activity. The studied microemulsion formulations have a prospect for use as a potential vehicle for treatment of UV B induced skin cancer. 相似文献
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The synthetic retinoid N-(4-hydroxphenyl) retinamide (4HPR) has manifold actions, which may contribute to its chemopreventive effects on breast cancer cell growth and progression. A role for ceramide as a stress-response signal is investigated here during the cytotoxic action of 4HPR in MCF-7 cells. N-(4-hydroxphenyl) retinamide induced a dose-dependent decline in cell growth and survival associated with a maximal 10-fold increase in ceramide production at 10 microM. N-(4-hydroxphenyl) retinamide exhibited a greater potency than all-trans retinoic acid (ATRA) on growth inhibition and ceramide production. The synthetic peroxisome proliferator-activated receptors agonist troglitazone (TGZ), but not the native ligand 15-deoxy-delta 12,14-prostaglandin J2, abrogated both these actions of 4HPR but not that of ATRA. The antioxidant N-acetylcysteine mimicked the abrogative effect of TGZ on 4HPR action, while the exogenous oxidant H2O2 also stimulated ceramide production. The inhibitors of de novo ceramide synthesis, fumonisin B1 and myriocin, blocked the ceramide response to 4HPR and partially reversed the apoptotic response, but did not prevent the overall decline in cell survival. The pancaspase inhibitor Z-VAD fmk reduced the decrease in cell survival caused by 4HPR, but did not affect the ceramide response. These findings describe a novel redox-sensitive elevation of ceramide levels associated with the cytotoxic response of breast cancer cells to 4HPR. However, a major mediatory role for this sphingolipid in this context remains equivocal. 相似文献
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Murugesan N Gu Z Spergel S Young M Chen P Mathur A Leith L Hermsmeier M Liu EC Zhang R Bird E Waldron T Marino A Koplowitz B Humphreys WG Chong S Morrison RA Webb ML Moreland S Trippodo N Barrish JC 《Journal of medicinal chemistry》2003,46(1):125-137
We have previously disclosed the selective ET(A) receptor antagonist N-(3,4-dimethyl-5-isoxazolyl)-4'-(2-oxazolyl)[1,1'-biphenyl]-2-sulfonamide (1, BMS-193884) as a clinical development candidate. Additional SAR studies at the 2'-position of 1 led to the identification of several analogues with improved binding affinity as well as selectivity for the ET(A) receptor. Following the discovery that a 3-amino-isoxazole group displays significantly improved metabolic stability in comparison to its 5-regioisomer, the 3-amino-isoxazole group was combined with the optimal 2'-substituent leading to 16a (BMS-207940). Compound 16a is an extremely potent (ET(A) K(i) = 10 pM) and selective (80,000-fold for ET(A) vs ET(B)) antagonist. It is also 150-fold more potent and >6-fold more selective than 1. The bioavailability of 16a was 100% in rats and the systemic clearance and volume of distribution are higher than that of 1. In rats, intravenous 16a blocks big ET pressor responses with 30-fold greater potency than 1. After oral dosing at 3 micromol/kg, 16a displays enhanced duration relative to 1. 相似文献