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991.
Cenedella RJ Jacob R Borchman D Tang D Neely AR Samadi A Mason RP Sexton P 《Journal of lipid research》2004,45(7):1232-1241
Induction of cataracts in experimental animals is a common toxic feature of oxidosqualene cyclase (OSC) inhibitors. U18666A has been shown to produce irreversible lens damage within a few weeks of treatment. Drug actions, besides reducing the availability of cholesterol, could contribute to cataract formation. Cholesterol added to cultures of lens epithelial cells could only partially overcome the growth-inhibiting effects of U18666A. In view of this finding and the fact that U18666A and other OSC inhibitors are highly lipophilic cationic tertiary amines, we tested the hypothesis that the cataractogenic effect of U18666A is related to direct perturbation of lens membrane structure and function. Based on changes in the anisotropy of fluorescent probes, U18666A incorporated into bovine lens lipid model membranes increased membrane structural order and, using small-angle x-ray diffraction, U18666A was shown to intercalate into the lens lipid model membranes and produce a broad condensing effect on membrane structure. Also, exposure of cultured lens epithelial cells and intact rat lenses to U18666A induced apoptosis. Induction of apoptosis may begin by intercalation of U18666A into cell membranes. By increasing membrane structural order, U18666A may also increase light scatter, thus directly contributing to lens opacification. 相似文献
992.
Nasser M. Al-Daghri Lotfi S. Bindahman Omar S. Al-Attas Tahia H. Saleem Majed S. Alokail Khalid M. Alkharfy Hossam M. Draz Sobhy Yakout Amany O. Mohamed Alison L. Harte Philip G. McTernan 《PloS one》2012,7(12)
Central adiposity is a significant determinant of obesity-related hypertension risk, which may arise due to the pathogenic inflammatory nature of the abdominal fat depot. However, the influence of pro-inflammatory adipokines on blood pressure in the obese hypertensive phenotype has not been well established in Saudi subjects. As such, our study investigated whether inflammatory factors may represent useful biomarkers to delineate hypertension risk in a Saudi cohort with and without hypertension and/or diabetes mellitus type 2 (DMT2). Subjects were subdivided into four groups: healthy lean controls (age: 47.9±5.1 yr; BMI: 22.9±2.1 Kg/m2), non-hypertensive obese (age: 46.1±5.0 yr; BMI: 33.7±4.2 Kg/m2), hypertensive obese (age: 48.6±6.1 yr; BMI: 36.5±7.7 Kg/m2) and hypertensive obese with DMT2 (age: 50.8±6.0 yr; BMI: 35.3±6.7 Kg/m2). Anthropometric data were collected from all subjects and fasting blood samples were utilized for biochemical analysis. Serum angiotensin II (ANG II) levels were elevated in hypertensive obese (p<0.05) and hypertensive obese with DMT2 (p<0.001) compared with normotensive controls. Systolic blood pressure was positively associated with BMI (p<0.001), glucose (p<0.001), insulin (p<0.05), HOMA-IR (p<0.001), leptin (p<0.01), TNF-α (p<0.001) and ANG II (p<0.05). Associations between ANG II and TNF-α with systolic blood pressure remained significant after controlling for BMI. Additionally CRP (p<0.05), leptin (p<0.001) and leptin/adiponectin ratio (p<0.001) were also significantly associated with the hypertension phenotype. In conclusion our data suggests that circulating pro-inflammatory adipokines, particularly ANG II and, TNF-α, represent important factors associated with a hypertension phenotype and may directly contribute to predicting and exacerbating hypertension risk. 相似文献
993.
Irina Nesterenko Simone Wanningen Tugba Bagci-Onder Maarten Anderegg Khalid Shah 《PloS one》2012,7(11)
Mesenchymal stem cells (MSC) are emerging as novel cell-based delivery agents; however, a thorough investigation addressing their therapeutic potential in medulloblastomas (MB) has not been explored to date. In this study, we engineered human MSC to express a potent and secretable variant of a tumor specific agent, tumor necrosis factor-apoptosis-inducing ligand (S-TRAIL) and assessed the ability of MSC-S-TRAIL mediated MB killing alone or in combination with a small molecule inhibitor of histone-deacetylase, MS-275, in TRAIL-sensitive and -resistant MB in vitro and in vivo. We show that TRAIL sensitivity/resistance correlates with the expression of its cognate death receptor (DR)5 and MSC-S-TRAIL induces caspase-3 mediated apoptosis in TRAIL-sensitive MB lines. In TRAIL-resistant MB, we show upregulation of DR4/5 levels when pre-treated with MS-275 and a subsequent sensitization to MSC-S-TRAIL mediated apoptosis. Using intracranially implanted MB and MSC lines engineered with different combinations of fluorescent and bioluminescent proteins, we show that MSC-S-TRAIL has significant anti-tumor effects in mice bearing TRAIL-sensitive and MS-275 pre-treated TRAIL-resistant MBs. To our knowledge, this is the first study that explores the use of human MSC as MB-targeting therapeutic-vehicles in vivo in TRAIL-sensitive and resistant tumors, and has implications for developing effective therapies for patients with medulloblastomas. 相似文献
994.
Aghayan HR Arjmand B Norouzi-Javidan A Saberi H Soleimani M Tavakoli SA Khodadadi A Tirgar N Mohammadi-Jahani F 《Cell and tissue banking》2012,13(2):281-285
Clinical grade cultivation of human schwann cell by the utilization of human autologous serum instead of fetal bovine serum, and also avoiding any growth factors, can increase safety level of this procedure in cases of clinical cell transplantation. The aim of this study was demonstration of the feasibility of clinical grade schwann cell cultivation. In this experimental study after obtaining consent from close relatives we harvested 10 sural nerves from brain death donors and then cultured in 10 seperated culture media plus autologous serum. We also prepared autologous serum from donor??s whole blood. Then cultured cells were evaluated by S100 antibody staining for both morphology and purity. Cell purity range was from 97% to 99% (mean?=?98.11?±?0.782%). Mean of the cell count was 14,055.56?±?2,480.479 per micro liter. There was not significant correlation between cell purity and either the culture period or the age of donors (P?>?0.05). The spearman correlation coefficient for the cell purity with the period or the age of donors was 0.21 and 0.09, respectively. We demonstrated the feasibility of clinical grade schwann cell cultivation by the using of human autologous serum instead of fetal bovine serum and also without the using of growth factors. We also recommended all cell preparation facilities to adhere to the GMP and other similar quality disciplines especially in the preparation of clinically-used cell products. 相似文献
995.
Rahimi Z Ahmadian Z Akramipour R Vaisi-Raygani A Rahimi Z Parsian A 《Molecular biology reports》2012,39(3):2195-2200
In order to determine the influence of polymorphism in thymidylate synthase (TS 28-bp repeat) and methionine synthase (MS
A2756G) genes on the susceptibility to acute lymphoblastic leukemia (ALL), 73 children with ALL and 128 age and sex matched
unrelated healthy individuals from the Kermanshah Province of Iran were screened. The genotyping of TS 28-bp repeat and MS
A2756G polymorphisms were performed by polymerase chain reaction (PCR) and PCR–RFLP, respectively. The frequency of TS 2R
allele in patients and controls were 41.5 and 38%, respectively (Odds ratios (OR) = 1.13, 95%CI 0.73–1.74, P = 0.56). The allelic frequency of G allele of MS was higher (25%) in patients compared with healthy subjects (23%) (OR = 1.09,
95%CI 0.67–1.75, P = 0.71). Considering MS AA and TS 3R3R genotypes as reference indicated that individuals with MS GG + TS 2R2R genotypes have
1.3-fold increase in the risk of ALL (OR = 1.3, 95%CI 0.6–2.7, P = 0.5). Our results showed that neither TS 28-bp repeat nor MS A2756G polymorphisms are risk factors for susceptibility to
ALL in Western Iran. 相似文献
996.
Sadegh Satarifard Abbas Ali GaeiniSiroos Choobineh Leila Shafiei Neek 《Journal of thermal biology》2012
The purpose of this study was to determine the effects of acute exercise on IL-17 concentrations in hot and neutral environments in trained males. Ten trained, non-heat acclimated males performed two 1 h run on treadmill at 60% VO2max in neutral (22±1 °C, 50±5RH) and hot (35±1 °C, 50±5) temperature conditions. Samples of the venous blood were taken (Pre, post, 2 h post) for determination of serum IL-17, cortisol concentrations and numbers of leukocytes and neutrophils. In addition, body temperature, RPE and PVC during exercise were measured. The collected data were analyzed using the Repeated-Measures analyses of variance and Bonferroni post hoc and Paird T tests (p<0.05). The concentration of cortisol and total number of leukocytes increased significantly after exercise, in both conditions (p<0.0001) and were significantly higher in hot than neutral (p=0.016, p=0.002). During the rest period (2 h post) the number of neutrophils increased significantly in hot environment (p=0.018). The concentrations of IL-17 increased significantly only after exercise in hot (p<0.0001) and were significantly higher during hot than neutral (p=0.002). The results suggest that exercise in hot environment cause increase in body temperature, perceived exertion and cardiac-vascular changes which are sufficient to elicit immune, hormonal and inflammatory responses. The present results confirm the additive effect of heat stress on the IL-17 response during exercise. 相似文献
997.
Human milk is usually the only source of food for infants during the first 4 to 5 months of their life. In this research, 80 human milk samples were collected from mothers in Tehran, Noushahr and the countryside of Tabriz, Iran, who were not occupationally exposed to mercury. The mean concentration of mercury in breast milk obtained from mothers in the countryside of Tabriz, Noushahr and Tehran was 0.86, 0.15 and 0.12 μg/L, respectively. There was a significant difference in mercury concentration in human breast milk between that from the countryside of Tabriz with that from Tehran and Noushahr. Only 3.7% of infant samples (three infants) had mercury concentration higher than normal versus the WHO recommended limit (0.5 μg g(-1)). The fish consumption of these mothers in Tehran and Noushahr was a factor that significantly affected the mercury concentration in their breast milk. Also, their age affected the mercury levels in breast milk (p = 0.04). 相似文献
998.
999.
ABSTRACT: BACKGROUND: The pyrethroid class of insecticides, including deltamethrin, is being used as substitutes for organochlorines and organophosphates in pest-control programs because of their low environmental persistence and toxicity. This study was aimed to investigate the impact of commonly used pesticides (deltamethrin) on the blood and tissue oxidative stress level in catfish (Clarias gariepinus); in addition to the protective effect of alpha-tocopherol on deltamethrin induced oxidative stress. METHODS: Catfish were divided into three groups, 1st control group include 20 fish divided into two tanks each one contain 10 fish, 2nd deltamethrin group, where Fish exposed to deltamethrin in a concentration (0.75ug/l) and 3rd Vitamin E group, Fish exposed to deltamethrin and vitamin E at a dose of 12ug/l for successive 4 days. Serum, liver, kidney and Gills were collected for biochemical assays. Tissue oxidative stress biomarkers malondialdhyde (MDA) and catalase activity in liver, kidney and gills tissues, serum liver enzymes (ALT and AST), serum albumin, total protein, urea and creatinine were analysed. RESULTS: Our results showed that 48 h. exposure to 0.75 ug/l deltamethrin significantly (p<0.05) increased lipid peroxidation (MDA) in the liver, kidney and gills while catalase activity was significantly decreased in the same tissues. This accompanied by significant increase in serum ALT, AST activity, urea and creatinine and a marked decrease in serum albumin and total proteins. CONCLUSIONS: It could be concluded that deltamethrin is highly toxic to catfish even in very low concentration (0.75 ug/l). Moreover the effect of deltamethrin was pronounced in the liver of catfish in comparison with kidneys and gills. Moreover fish antioxidants and oxidative stress could be used as biomarkers for aquatic pollution, thus helping in the diagnosis of pollution. Adminstration of 12 ug/l alpha-tocopherol restored the quantified tissue and serum parameters, so supplementation of alpha-tocopherol consider an effective way to counter the toxicity of deltamethrin in the catfish. 相似文献
1000.
van Ganzewinkel CJ Mohns T van Lingen RA Derijks LJ Andriessen P 《Journal of medical case reports》2012,6(1):1-5