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71.
Delfín DA Bhattacharjee AK Yakovich AJ Werbovetz KA 《Journal of medicinal chemistry》2006,49(14):4196-4207
A 3D pharmacophore was generated to describe the antileishmanial activity of dinitroaniline sulfonamides by CATALYST 3D-QSAR methodology, and this pharmacophore was used to search the Maybridge database. Two compounds identified in this search, BTB 06237 and BTB 06256, were highly active with IC(50) values against L. donovani amastigotes of 0.5 +/- 0.2 and 2.3 +/- 0.8 microM, respectively. BTB 06237 also reduced parasite burdens in L. mexicana-infected J774 macrophages at low micromolar concentrations. Unlike the dinitroaniline sulfonamides, the active compounds did not display antimitotic effects against Leishmania. Transmission electron microscopy showed that the single parasite mitochondrion becomes dilated following incubation with BTB 06237, and fluorescence microscopy demonstrated that this organelle fragments into intensely staining spheres when treated with a mitochondrion-specific dye. The mitochondrial membrane potential was also dissipated in BTB 06237-treated parasites. These results indicate that BTB 06237 is an intriguing antileishmanial lead compound that likely interferes with mitochondrial function. 相似文献
72.
We reported previously that 3-hydroxy-3-methylglutaryl coenzyme A reductase synthesis is regulated at the translational level by mevalonate. To determine at what stage mevalonate affects reductase synthesis, we examined the distribution of reductase mRNA in polysomes from cells treated with lovastatin alone; lovastatin and 25-hydroxycholesterol; or lovastatin, 25-hydroxycholesterol, and mevalonate. In lovastatin-treated cells, reductase mRNA was primarily associated with heavy polysome fractions. When 25-hydroxycholesterol was added to lovastatin-treated cells, reductase mRNA levels were reduced approximately fourfold in all polysome fractions, with no accompanying redistribution of reductase mRNA into lighter polysome fractions. However, addition of both 25-hydroxycholesterol and mevalonate to lovastatin-treated cells shifted reductase mRNA from heavier to lighter polysome fractions. No change in the distribution of control -actin or ribosomal protein S17 mRNA occurred with any of the treatment. These results suggest that mevalonate suppresses reductase synthesis at the level of initiation. When the translation inhibitor cycloheximide was added to all three regimens, reductase mRNA shifted into heavy polysome fractions. Treatment with either lovastatin alone or lovastatin plus 25-hydroxycholesterol resulted in a 50% greater loss of reductase mRNA from the heavy polysome fractions compared to the same fractions from noncycloheximide-treated cells. No loss of reductase mRNA occurred when cycloheximide was added to cells treated with both 25-hydroxycholesterol and mevalonate. -Actin mRNA levels and polysome distribution were not significantly changed by cycloheximide under any of these conditions. Translationally mediated suppression of reductase mRNA did not occur when protein synthesis was inhibited with puromycin. Our results indicate that regulation of reductase mRNA levels is translation-dependent and is linked to the rate of elongation. 相似文献
73.
EPIDEMIC OF HAND, FOOT AND MOUTH DISEASE IN WEST BENGAL, INDIA IN AUGUST, 2007: A MULTICENTRIC STUDY
Nilendu Sarma Abhijit Sarkar Amlan Mukherjee Apurba Ghosh Sandipan Dhar Rajib Malakar 《Indian journal of dermatology》2009,54(1):26-30
Background:
Hand, foot, and mouth disease (HFMD) is caused mostly by Coxsackievirus A16 (CA16) and enterovirus 71 (EV71). Epidemic of HFMD has occurred in India only once in Kerala in 2003. We report here a recent outbreak of HFMD in three districts of West Bengal, India.Materials and Methods:
A case detection system developed with 1) three private clinics in three districts; two at Howrah and one at Hooghly, 2) Pediatrics Department of two medical colleges in Kolkata, 3) 12 practioners of these three districts with 4) a central referral center at Department of Dermatology, NRS Medical College, Kolkata where all cases from this system were confirmed by a single observer. Pediatric Dermatology unit of the Institute of Child Health, Kolkata was another independent unit.Results:
A total of 38 cases of HFMD were reported till 08.10.07. Age group ranged from 12 months to 12 years (mean 40.76 months, SD 29.49). Males were slightly higher than females (M:F - 21:17). Disease was distributed mostly over buttocks, knees, hands, feet - both dorsum and palmar or the plantar surface and the oral mucosa. Highest severity noted over the buttocks and the knee. Healing time for skin lesions was 6-13 days (mean 9.13 days, SD 1.93). Oral lesions were found in 33 (86.8%) cases.Conclusion:
This outbreak far away from the initial one confirmed regular outsourcing of the virus with possibilities of future epidemics. Also the fact that EV71 induced epidemic is on rise in this part of globe is alarming for India. We hope this early report will be of help for strategic planning for a better management of the disease and prevention of dreaded neurological complications in India. 相似文献74.
Jhuma Biswas Picklu Chaudhuri Apurba Mandal Sambhu Nath Bandyopadhyay Shyamal Dasgupta Anirban Pal 《International journal of gynaecology and obstetrics》2013
Objective
To investigate whether use of preoperative misoprostol can reduce blood loss during total abdominal hysterectomy (TAH).Methods
In a randomized double-blind placebo-controlled trial at a tertiary care hospital in Kolkata, India, between March 2011 and April 2012, women (n = 132) undergoing TAH with or without bilateral salpingo-oophorectomy for symptomatic myomas were randomly allocated to receive either 400 μg of misoprostol or placebo 30 minutes before surgery. The primary outcome measure was intraoperative blood loss was. The secondary outcomes were postoperative drop in hemoglobin, need for blood transfusion, and incidence of adverse effects.Results
The 2 groups were similar with regard to demographic and clinical characteristics. There was a significant reduction of blood loss during TAH after sublingual administration of misoprostol compared with placebo before surgery (356 mL vs 435 mL; P = 0.049). The mean postoperative hemoglobin concentration was higher (10.5 g/dL vs 9.5 g/dL; P < 0.001) and the postoperative drop in hemoglobin was smaller (1.1 g/dL vs 1.9 g/dL; P = 0.004) in the misoprostol group than in the placebo group. No significant adverse effects occurred in either group.Conclusion
The results showed that a single dose of misoprostol administered before abdominal hysterectomy resulted in a significant reduction of blood loss with minimal adverse effects.Clinical Trial Registry India (www.ctri.nic.in): CTRI/2011/091/000216. 相似文献75.
Ghosh A Ghosh SK Bhattacharyya SK Kothari R Kabasi A 《Journal of the Indian Medical Association》2010,108(4):212-214
Eighty-three cases of carcinoma of the cervix presenting over a 5-year period, 1997 to 2001 were considered for evaluation of the effects of Irradiation on the urinary tract. Ultrasound scans were used to detect ureteric obstructions in the follow-up period. Significant progressive ureteric obstruction occurred in 6 patients (7.2%), all of whom had malignant strictures. The diagnoses of these strictures were made between 8 months and five years after the Initial treatment. Patients having malignant stricture tend to be in a higher original stage of tumour. The lower ureter was the site of ureteric obstruction in 4 patients while 2 had lesions in middle ureter. The latency period between primary treatment of the tumour and diagnosis of uropathy is significantly shorter for malignant strictures. The site of occurrence of the strictures had no discernible significance but the absence of a bilateral obstruction in spite of all of them being malignant lesions is in disagreement with the published data. 相似文献
76.
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78.
Prabhas Prasun Giri Priyankar Pal Apurba Ghosh Rajiv Sinha 《Rheumatology international》2013,33(5):1363-1366
Haemophagocytic lymphohistiocytosis (HLH) is a heterogeneous group of clinical syndromes characterised by activation and subsequent uncontrolled non-malignant proliferation of T lymphocytes and macrophages, leading to a cytokine storm that accounts for most of its clinical features such as acute febrile illness, hepatosplenomegaly, multi-organ dysfunction and fulminant pancytopenia-resembling severe sepsis. Here, we present a series of 23 cases of infection-associated HLH diagnosed in our hospital within a time period of last three and half years. Though the presentation and progression of disease was variable, the patients shared some common features like prolonged fever unresponsive to broad spectrum antibiotics, organomegaly and cytopenias. In most of the cases, however, the triggering infectious agent could not be identified. They were treated using a steroid only protocol along with supportive measures and showed an excellent response. 相似文献
79.
Asnani M Vyas K Bhattacharya A Devarakonda S Chakraborty S Mukherjee AK 《Journal of pharmaceutical sciences》2009,98(6):2113-2121
Sodium alendronate, a member of bisphosphonate class of compounds commonly used for treatment of generalized bone disorders, exists in various hydrated forms. Dehydration of sodium alendronate trihydrate has been studied using variable temperature X-ray powder diffraction technique. The crystal structure of anhydrous sodium alendronate, prepared by heating the trihydrate sodium alendronate at 150 degrees C, has been determined from X-ray powder data using direct space global optimization technique for structure solution, followed by the Rietveld refinement. The structure of the anhydrous form of sodium alendronate is compared with that of the trihydrate form, which was determined previously from single crystal X-ray diffraction data. Both anhydrous and trihydrate sodium alendronate crystallize in monoclinic system with space group P2(1)/n. The crystal structure of the anhydrous sodium alendronate is built by edge-sharing of NaO(6) octahedra into a two-dimensional molecular sheet in the (011) plane, whereas in the trihydrate compound, one-dimensional chain along the (010) direction is generated by corner sharing of NaO(6) octahedra. 相似文献
80.
The antimalarial potential of 4-quinolinecarbinolamines may be limited due to neurotoxicity and cross-resistance in mefloquine-resistant Plasmodium falciparum strains 下载免费PDF全文
Dow GS Koenig ML Wolf L Gerena L Lopez-Sanchez M Hudson TH Bhattacharjee AK 《Antimicrobial agents and chemotherapy》2004,48(7):2624-2632
The clinical potential of mefloquine has been compromised by reports of adverse neurological effects. A series of 4-quinolinecarbinolamines were compared in terms of neurotoxicity and antimalarial activity in an attempt to identify replacement drugs. Neurotoxicity (MTT [thiazolyl blue reduction] assay) was assessed by exposure of cultured embryonic rat neurons to graded concentrations of the drugs for 20 min. The 50% inhibitory concentration (IC(50)) of mefloquine was 25 microM, while those of the analogs were 19 to 200 microM. The relative (to mefloquine) therapeutic indices of the analogs were determined after using the tritiated hypoxanthine assay for assessment of the antimalarial activity of the analogs against mefloquine-sensitive (W2) and -resistant (D6 and TM91C235) Plasmodium falciparum strains. Five analogs, WR157801, WR073892, WR007930, WR007333, and WR226253, were less neurotoxic than mefloquine and exhibited higher relative therapeutic indices (RTIs) against TM91C235 (2.9 to 12.2). Conventional quinoline antimalarials were generally less neurotoxic (IC(50)s of 400, 600, and 900 for amodiaquine, chloroquine, and quinine) or had higher RTIs (e.g., 30 for halofantrine against TM91C235). The neurotoxicity data for the 4-quinolinecarbinolamines were used to develop a three-dimensional (3D), function-based pharmacophore. The crucial molecular features correlated with neurotoxicity were a hydrogen bond acceptor (lipid) function, an aliphatic hydrophobic function, and a ring aromatic function specifically distributed in the 3D surface of the molecule. Mapping of the 3D structures of a series of structurally diverse quinolines to the pharmacophore allowed accurate qualitative predictions of neurotoxicity (or not) to be made. Extension of this in silico screening approach may aid in the identification of less-neurotoxic quinoline analogs. 相似文献