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51.
Synthesis of primaquine glyco‐conjugates as potential tissue schizontocidal antimalarial agents
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Chandra S. Azad Mridula Saxena Arif J. Siddiqui Jyoti Bhardwaj Sunil K. Puri Guru P. Dutta Nitya Anand Anil K. Saxena 《Chemical biology & drug design》2017,90(2):254-261
Primaquine ( PQ ) is the only drug used to prevent relapse of malaria due to P. vivax and P. ovale, by eradicating the dormant liver form of the parasite (hypnozoites). The side‐effects associated with PQ limits is uses in treatment of malaria. To overcome the premature oxidative deamination and to increase the life span of drug in the biological system, the novel glyco‐conjugates of PQ were synthesized by coupling of primaquine with hexoses in phosphate buffer. The saccharide part of the hybrid molecules thought to direct the drug to the liver, where hypnozoites resides. All the synthesized compounds were fully characterized and evaluated for their radical curative activities. The three compounds viz glucoside ( 15a ), galactoside ( 15b ) and mannoside ( 15c ) with high activity were tested for their activity in rhesus monkeys where the most active compound 15b showed twofold activity (100% radical curative activity at 1.92 mmol/kg) than the standard drug PQ diphosphate (3.861 mmol/kg). It is proposed that results from these studies may be advantageous to develop a new potent tissue schizonticide antimalarial compound. 相似文献
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Swati Bhardwaj Ranjeet Thergaonkar Aditi Sinha Pankaj Hari Cheong Hi Arvind Bagga 《Indian pediatrics》2016,53(11):977-982
Objective
To describe the clinical and genotypic features of Dent disease in children diagnosed at our center over a period of 10 years.Design
Case series.Setting
Pediatric Nephrology Clinic at a referral center in Northern India.Methods
The medical records of patients with Dent disease diagnosed and followed up at this hospital from June 2005 to April 2015 were reviewed. The diagnosis of Dent disease was based on presence of all three of the following: (i) low molecular weight proteinuria, (ii) hypercalciuria and (iii) one of the following: nephrolithiasis, hematuria, hypophosphatemia or renal insufficiency, with or without mutation in CLCN5 or OCRL1 genes.Results
The phenotype in 18 patients diagnosed with Dent disease during this period was characterized by early age at onset (median 1.8 y), and polyuria, polydipsia, salt craving, hypophosphatemic rickets and night blindness. Rickets was associated with severe deformities, fractures or loss of ambulation in six patients. Nephrocalcinosis was present in three patients, while none had nephrolithiasis. Generalized aminoaciduria was seen in 13 patients, two had glucosuria alone, and one had features of Fanconi syndrome. Over a median follow up of 2.7 years, one patient developed renal failure. Genetic testing (n=15) revealed 5 missense mutations and 3 nonsense mutations in CLCN5 in 13 patients. Five of these variations (p.Met504Lys, p.Trp58Cys, p.Leu729X, p.Glu527Gln and p.Gly57Arg) have not been reported outside the Indian subcontinent.Conclusion
Our findings suggest a severe phenotype in a cohort of Indian patients with Dent disease.55.
Sanjay Kalra Palash Aiyer Minakshi Bhardwaj Vijay Grover Vijay Kumar Gupta 《Indian Journal of Thoracic and Cardiovascular Surgery》2016,32(2):113-119
Purpose
The great saphenous vein harvested with a traditional open technique often results in leg wound complications. An endoscopic harvesting technique may decrease incidence of these complications.Methods and material
Fifty consecutive patients having elective primary coronary artery bypass surgery were prospectively and randomly assigned to either endoscopic great saphenous vein harvesting (EVH—group A) or open great saphenous vein harvesting (OVH—group B). Both groups were demographically similar and received identical management. Leg wound healing was evaluated at discharge, 1 week, 1 month and 6 months for evidence of complications.Result
The patient in endoscopic vein harvesting group had increased harvest time and an insignificant increase in vein injuries at the time of harvesting but decreased incision closure times when compared with traditional longitudinal open vein harvesting. Conversion from endoscopy to a traditional longitudinal open vein harvest occurred in 5 % of patients. Leg wound complications were significantly reduced postoperatively in the endoscopic vein harvesting group in comparison with the open vein harvesting group. Histological evaluation of structural integrity of vein samples shows that there is no significant difference between both the groups. No patient was readmitted to the hospital for leg wound complications in either group.Conclusion
EVH is a safe, reliable method for saphenous vein harvesting. The best indication for EVH may be in patients who are in increased risk for wound infection and in whom cosmetics is a major concern.56.
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OBJECTIVE: Because of their beneficial effects in patients with hemorrhagic shock and multiple-system trauma, hypertonic saline solutions are increasingly being used perioperatively for volume resuscitation. Although the anti-edema effects of hypertonic saline on brain are well documented in a variety of brain injury paradigms, its effects on the water content on other organs has not been studied rigorously. In this study, we tested the hypothesis that a) hypertonic saline when given as an intravenous bolus and continuous infusion attenuates water content of small bowel, lung, and brain in rats without neuro-injury; and b) attenuation of stroke-associated increases in lung water is dependent on achieving a target serum osmolality. DESIGN: Prospective laboratory animal study. SETTING: Research laboratory in a teaching hospital. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: In the first series of experiments, under controlled conditions of normoxia, normocarbia, and normothermia, spontaneously breathing, halothane-anesthetized (1.0-1.5%) adult male Wistar rats (280-320 g) were treated in a blinded randomized fashion with 7.5% hypertonic saline or 0.9% normal saline in a 8-mL/kg intravenous infusion for 3 hrs followed by a continuous intravenous infusion (1 mL/kg/hr) of 5% hypertonic saline or normal saline, respectively (n=10 each), for 48 hrs. A second group of rats were treated with continuous infusion only for 48 hrs of either 7.5% hypertonic saline or normal saline (1 mL/kg/hr) (n=10 each) without an intravenous bolus. Na?ve rats served as controls (n=10). Tissue water content of small bowel, lung, and brain was determined by comparing the wet-to-dry ratios at the end of the experiment. In a second series of experiments, rats (n=94) were subjected to 2 hrs of transient middle cerebral artery occlusion by the intraluminal occlusion technique. At 6 hrs following middle cerebral artery occlusion, rats were treated in a blinded randomized fashion with a continuous intravenous infusion of normal saline, 3% hypertonic saline, or 7.5% hypertonic saline for 24, 48, 72, and 96 hrs. Surgical shams served as controls (n=7). Hypertonic saline was instituted as chloride/acetate mixture (50:50) in all experiments. Serum osmolality was determined at the end of the experiment in all animals. MEASUREMENTS AND MAIN RESULTS: In rats without neuro-injury that received intravenous bolus followed by a continuous infusion, lung water content was significantly reduced with hypertonic saline (73.9+/-1.1%; 359+/-10 mOsm/L) (mean+/-sd) compared with normal saline treatment (76.1+/-0.53%; 298+/-4 mOsm/L) as was water content of small bowel (hypertonic saline, 69.1+/-5.8%; normal saline, 74.7+/-0.71%) and brain (hypertonic saline, 78.1+/-0.87%; normal saline, 79.2+/-0.38%) at 48 hrs. Stroke-associated increases in lung water content were attenuated with 7.5% hypertonic saline at all time points. There was a strong correlation between serum osmolality and attenuation of stroke-associated increases in lung water content (r=-.647) CONCLUSIONS: Bowel, lung, and brain water content is attenuated with hypertonic saline when serum osmolality is >350 mOsm/L without adverse effect on mortality in animals with and without neuro-injury. Attenuation of water content of extracerebral organs with hypertonic saline treatment may have therapeutic implications in perioperative fluid management in patients with and without brain injury. 相似文献
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Glucocorticoid therapy in neurologic critical care 总被引:10,自引:0,他引:10
BACKGROUND: The pivotal role of inflammation and edema across the spectrum of central nervous system injury has driven extensive investigation into the therapeutic potential of glucocorticoids. OBJECTIVE: To review the experimental and clinical data relating to the efficacy and adverse effects of glucocorticoids in conditions encountered in critical neurologic and neurosurgical illness. DATA SOURCE: Search of MEDLINE and Cochrane databases, manual review of article bibliographies. DATA SYNTHESIS AND CONCLUSIONS: The efficacy of glucocorticoids is well established in ameliorating edema associated with brain tumors and in improving outcome in subsets of patients with bacterial meningitis. Despite frequently encouraging experimental results, clinical trials of glucocorticoids in ischemic stroke, intracerebral hemorrhage, aneurysmal subarachnoid hemorrhage, and traumatic brain injury have not shown a definite therapeutic effect. The evidence supporting glucocorticoid therapy for spinal cord injury is controversial; however methylprednisolone continues to be widely employed in this setting. 相似文献
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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