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41.
Deepali Gupta Surjit Singh Deepti Suri Jasmina Ahluwalia Reena Das Neelam Varma 《Rheumatology international》2010,30(6):767-770
The objectives of this study are to highlight the arthritic presentation of acute lymphoblastic leukemia (ALL) in children
and to delineate features that could help differentiate it from juvenile idiopathic arthritis (JIA). We present a retrospective
case control study based on records of the Pediatric Rheumatology Clinic, Advanced Pediatric Centre, Post Graduate Institute
of Medical Education and Research, Chandigarh, India for the period January 2005–October 2008. We compared the clinical profile
of 11 children referred to us with musculoskeletal complaints who were ultimately diagnosed to have ALL, with the clinical
profile of an equal number of age and sex matched children with JIA. Important features that predicted a diagnosis of ALL
and differentiated it from JIA were history of night pain (P = 0.001), non-articular bony pain (P = 0.001), presence of joint pain out of proportion to physical findings (P = 0.0001), anemia (P = 0.004), leucopenia (P = 0.045), lymphocytic predominance (P = 0.002) and thrombocytopenia (P = 0.012). In conclusion, children with musculoskeletal complaints are often referred to the rheumatologist for evaluation.
The treating physician should always exclude the possibility of an underlying ALL especially if there are atypical clinical
features or subtle hematological abnormalities. 相似文献
42.
In this study, the potential of lecithin/chitosan nanoparticles (NPs) as colloidal nanosystem for transdermal melatonin delivery was investigated. Mean diameter and zeta-potential of NPs differing in lecithin type (Lipoid S45 and S100) and chitosan content ranged between 113.7 and 331.5?nm and 4.6 and 31.2?mV, respectively. Melatonin loadings were up to 7.2%. The potential of lecithin/chitosan NPs to enhance transdermal melatonin delivery was investigated by determining the drug flux across dermatomed porcine skin and its skin deposition. Lecithin/chitosan NPs provided 1.3-2.3-fold higher flux compared to melatonin solution. The highest flux, 9.0?±?0.21?μg/cm2/h, was observed for S45 lecithin/chitosan NPs with lecithin/chitosan weight ratio of 20:1. NP possible cytotoxicity in vitro was evaluated using human skin keratinocytes and fibroblasts. It was demonstrated that lecithin/chitosan NPs can be applied to skin cells at concentrations up to 200?μg/mL without inducing plasma membrane damage or cell viability decrease. 相似文献
43.
Matovi? V Buha A Bulat Z Duki?-?osi? D Miljkovi? M Ivani?evi? J Kotur-Stevuljevi? J 《Food and chemical toxicology》2012,50(3-4):552-557
The study was designed to evaluate and compare the effects of single oral (or) and intraperitoneal (i.p.) cadmium (Cd) administration on parameters of oxidative stress in liver of rats. Furthermore, investigation on protective effects of magnesium (Mg) or and i.p. pretreatment on the same parameters was performed. Wistar rats were administrated oral dose of Cd (30 mg Cd/kg b.w.)/Cd+Mg (30 mg Cd/kg b.w., 50 mg Mg/kg b.w.) or i.p. dose of Cd (1.5 mg Cd/kg b.w.)/Cd+Mg (1.5 mg Cd/kg b.w., 3 mg Mg/kg b.w.) and sacrificed after 24 h. In liver homogenates superoxide anion, malondialdehyde, non-protein sulfhydryl groups, total sulfhydryl groups content, and superoxide dismutase activity were determined. Cadmium intoxication caused the increase of superoxide anion and malondialdehyde levels and had negative effect on investigated parameters of antioxidant defense system, except on total sulfhydryl groups. The negative effect was more emphasized after i.p. Cd administration. Oral Mg pretreatment induced more pronounced positive effect than Mg given intraperitoneally that can be attributed, at least partly, to Cd and Mg interactions on the level of GIT. On the basis of the obtained results it can be concluded that both Cd and Cd+Mg effects on parameters of oxidative stress in rats liver are route-dependent. 相似文献
44.
Garewal G Das R Awasthi A Ahluwalia J Marwaha RK 《European journal of haematology》2007,79(5):417-421
OBJECTIVES: To assess the clinical significance of the interactions of CAP+1 (A-->C), a silent beta-globin gene mutation, with other beta-thalassemia mutations and globin gene modifiers in north Indians. METHODS: The clinical phenotypes associated with compound heterozygosity for the CAP+1 (A-->C) mutation with other beta-thalassemia mutations, together with the potential effect of the genetic modifiers alpha-thalassemia and the Xmn-1(G)gamma C-->T polymorphism were studied in 30 patients. The frequency of the CAP+1 (A-->C) polymorphism was determined and an analysis of the red cell indices, HbA(2) levels, iron status, and alpha-globin genes was carried out in 35 heterozygotes. RESULTS: Based on an analysis of 1075 beta-thalassemia alleles the CAP+1 (A-->C) mutation constituted 3.2% of north Indians. There was a wide spectrum of phenotypic severity in compound heterozygotes; 18 of 30 were transfusion dependent. There was a very high frequency of the -/- genotype of the Xmn-1(G)gamma polymorphism in compound heterozygotes. Analysis of 35 heterozygotes indicated that approximately half were hematologically normal and therefore genuine 'silent' carriers. CONCLUSIONS: Compound heterozygotes for CAP+1 (A-->C) and other severe beta-thalassemia alleles are phenotypically severe enough to necessitate appropriate therapy and counseling. The unexpected severity of these interactions may be due, in part, to the high frequency of beta-thalassemia alleles associated with the Xmn-1(G)gamma- allele in Indian populations. It is concluded that the CAP+1 (A-->C) mutation can pose serious difficulties in screening and counseling programs in populations in which it occurs at a significant frequency. 相似文献
45.
46.
Jasmina Marjanovic Dominika Chalupska Caroline Patenode Adam Coster Evan Arnold Alice Ye George Anesi Ying Lu Ilya Okun Sergey Tkachenko Robert Haselkorn Piotr Gornicki 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(20):9093-9098
Acetyl-CoA carboxylase (ACC) is a key enzyme of fatty acid metabolism with multiple isozymes often expressed in different eukaryotic cellular compartments. ACC-made malonyl-CoA serves as a precursor for fatty acids; it also regulates fatty acid oxidation and feeding behavior in animals. ACC provides an important target for new drugs to treat human diseases. We have developed an inexpensive nonradioactive high-throughput screening system to identify new ACC inhibitors. The screen uses yeast gene-replacement strains depending for growth on cloned human ACC1 and ACC2. In “proof of concept” experiments, growth of such strains was inhibited by compounds known to target human ACCs. The screen is sensitive and robust. Medium-size chemical libraries yielded new specific inhibitors of human ACC2. The target of the best of these inhibitors was confirmed with in vitro enzymatic assays. This compound is a new drug chemotype inhibiting human ACC2 with 2.8 μM IC50 and having no effect on human ACC1 at 100 μM. 相似文献
47.
Jasmina Novakovic Angelo Tesoro Jake J Thiessen Michael Spino 《European journal of drug metabolism and pharmacokinetics》2004,29(4):221-224
A recently synthesized 3-hydroxypyridinone derivative with an amido function at the 2-position, CP502 (1,6-dimethyl-3-hydroxy-4-(1H)-pyridinone-2-carboxy-(N-methyl)-amide hydrochloride), exhibited high in vitro iron chelating potency (pFe3+ =21.7). It was targeted as a new iron-chelating candidate for further development in early pre-clinical testing. To evaluate its pharmacokinetics, including oral bioavailability, metabolic and disappearance profiles, studies were conducted in Sprague Dawley male rats. A single 150 mg/kg intravenous and oral dose was given to male Sprague Dawley rats (N=6, B.Wt. 250g). The rats were placed in metabolic cages and fasted overnight before the dosing. Venous blood samples (200 microL per withdrawal) were collected at defined time points before (blank) and up to 28 h post administration. Urine and feces were collected before dosing (blank) and in 24 h intervals up to 72 h post administration. Plasma CP502 concentration versus time profiles were consistent with two-compartment distribution, and the oral bioavailability approached 100%. Total clearance and mean residence time (i.v.) were 1.02 L/kg/h and 1.10 h, respectively. Simultaneous computer fitting yielded V1 and Vss estimates of 0.96 L/kg and 1.74 L/kg, respectively. CP502 was mainly excreted unchanged via urine (45.29+/-9.40 % of total dose) or as glucuronide (6.46+/-1.22% of total dose). High iron chelation potential and favorable pharmacokinetic and metabolic profiles indicate that CP502 is a promising candidate for further development. 相似文献
48.
Iskandar Idris Kunal Gulati Magaly Perez-Nieves Irene Hadjiyianni Dachuang Cao Arash Tahbaz Jasmina Ivanova Syed Wasi Hassan 《Primary Care Diabetes》2019,13(2):106-112
Aim
Real-world effectiveness of insulin therapy is affected by poor treatment persistence, often occurring soon after initiation. An international cross-sectional survey of people with type 2 diabetes mellitus (T2DM) has been conducted to describe reasons for non-persistence with insulin therapy.Methods
Responders to an online survey in 7 countries were classified as continuers (no gap of ≥7 days), interrupters (interrupted therapy for ≥7 days within first 6 months, then restarted), and discontinuers (terminated therapy for ≥7 days within first 6 months, no restart before survey). We present the results from the United Kingdom (UK) cohort.Results
Of 942 global respondents, 131 were from the UK, having a mean age of 37 years and a mean of 7 years since first T2DM diagnosis. Reasons contributing to insulin continuation (n = 50) were improved physical feeling (52.0%) and improved glycemic control (48.0%). Common reasons for interruption (n = 50) or discontinuation (n = 31), respectively were weight gain (50.0%, 48.4%) and hypoglycemia (38.0%, 25.8%). Most important reason for possible re-initiation for interrupters and discontinuers, respectively was persuasion by physician/healthcare professional (74.0%, 64.5%).Conclusion
The benefits of basal insulin therapy motivated continuers to persist with the treatment; experienced or anticipated side effects contributed to interruption and discontinuation. 相似文献49.
50.
Tamoxifen stimulates calcitonin-producing thyroid C-cells and prevents trabecular bone loss in a rat model of androgen deficiency 下载免费PDF全文
Branko Filipovi Branka oi‐Jurjevi Vladimir Ajdanovi Jasmina
ivanovi Esma Isenovi Florina Popovska‐Per
ini Verica Miloevi 《Journal of anatomy》2015,226(5):489-496
Thyroid C-cells produce calcitonin (CT), a hypocalcemic hormone, that acts as an inhibitor of bone resorption. In this study, we investigated the effects of tamoxifen (TAM) as a selective estrogen receptor modulator on thyroid C-cells, trabecular bone and biochemical markers of bone metabolism in an animal model of androgen deficiency, represented by middle-aged orchidectomized (Orx) rats. Fifteen-month-old male Wistar rats were divided into: Orx and sham-operated (SO) groups. Rats from one Orx group were injected subcutaneously with TAM citrate (Orx + TAM; 0.3 mg kg−1 b.w.), while the rats from SO and a second Orx group received vehicle alone, once a day for 3 weeks. The peroxidase–antiperoxidase method was applied for localization of CT in C-cells. Thyroid C-cells were morphometrically and ultrastructurally analyzed. An ImageJ image-processing program was used to measure bone histomorphometric parameters. Blood serum samples were analyzed for CT, osteocalcin (OC), calcium (Ca2+) and phosphorus (P). Urinary Ca2+ concentrations were measured. TAM treatment significantly increased thyroid C-cell volume (Vc) and serum CT when compared with vehicle-treated Orx rats. Analysis of trabecular microarchitecture of the tibia showed that administration of TAM significantly increased cancellous bone area, trabecular thickness and trabecular number, whereas trabecular separation was significantly decreased compared with vehicle-treated Orx rats. Serum OC and urinary Ca2+ concentrations were significantly lower in comparison with the control Orx group. These results indicate that in our rat model of androgen deficiency, TAM stimulated calcitonin-producing thyroid C-cells and increased trabecular bone mass. 相似文献