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排序方式: 共有288条查询结果,搜索用时 15 毫秒
41.
Mader M de Dios A Shih C Bonjouklian R Li T White W López de Uralde B Sánchez-Martinez C del Prado M Jaramillo C de Diego E Martín Cabrejas LM Dominguez C Montero C Shepherd T Dally R Toth JE Chatterjee A Pleite S Blanco-Urgoiti J Perez L Barberis M Lorite MJ Jambrina E Nevill CR Lee PA Schultz RC Wolos JA Li LC Campbell RM Anderson BD 《Bioorganic & medicinal chemistry letters》2008,18(1):179-183
Herein we report investigations into the p38alpha MAP kinase activity of trisubstituted imidazoles that led to the identification of compounds possessing highly potent in vivo activity. The SAR of a novel series of imidazopyridines is demonstrated as well, resulting in compounds possessing cellular potency and enhanced in vivo activity in the rat collagen-induced arthritis model of chronic inflammation. 相似文献
42.
A total of 188 yearling steers of predominantly Angus and Hereford breeds, with mean body weight of 299 kg, were used in this study, which started on 8 April and finished on 3 October, to assess the effects of environmental factors on feed intake of steers in various housing systems. Housing consisted of outside lots with access to overhead shelter, outside lots with no overhead shelter and a cold confinement building. Ad libitum corn, 2.27 kg of 35% dry matter whole plant sorghum silage and 0.68 kg of a 61% protein-vitamin-mineral supplement was offered. Feed that was not consumed was measured to determine feed intake. The temperature data were recorded by hygro-thermographs. Hourly temperatures and humidity were used to develop weather variables. Regression analysis was used and weather variables were regressed on dry matter intake (DMI). When addition of a new variable did not improve R (2) more than one unit, then the number of variables in the model was truncated. Cattle in confinement had lower DMI than those in open lots and those in open lots with access to an overhead shelter (P < 0.05). Cattle in outside lots with access to overhead shelter had similar DMI compared to those in open lots (P = 0.065). Effect of heat was predominantly displayed in August in the three housing systems. In terms of explaining variation in DMI, in outside lots with access to overhead shelter, average and daytime temperatures were important factors, whereas in open lots, nocturnal, peak and average temperatures were important factors. In confinement buildings, the previous day's temperature and humidity index were the most important factors explaining variation in DMI. Results show the effect of housing and weather variables on DMI in summer and when considering these results, cattle producers wishing to improve cattle feedlot performance should consider housing conditions providing less stress or more comfort. 相似文献
43.
44.
Coulson-Thomas VJ Coulson-Thomas YM Gesteira TF de Paula CA Mader AM Waisberg J Pinhal MA Friedl A Toma L Nader HB 《Cell and tissue research》2011,346(2):223-236
During cancer cell growth many tumors exhibit various grades of desmoplasia, unorganized production of fibrous or connective
tissue, composed mainly of collagen fibers and myofibroblasts. The accumulation of an extracellular matrix (ECM) surrounding
tumors directly affects cancer cell proliferation, migration and spread; therefore the study of desmoplasia is of vital importance.
Stromal fibroblasts surrounding tumors are activated to myofibroblasts and become the primary producers of ECM during desmoplasia.
The composition, density and organization of this ECM accumulation play a major role on the influence desmoplasia has upon
tumor cells. In this study, we analyzed desmoplasia in vivo in human colorectal carcinoma tissue, detecting an up-regulation of collagen I, collagen IV and collagen V in human colorectal
cancer desmoplastic reaction. These components were then analyzed in vitro co-cultivating colorectal cancer cells (Caco-2 and HCT116) and fibroblasts utilizing various co-culture techniques. Our findings
demonstrate that direct cell-cell contact between fibroblasts and colorectal cancer cells evokes an increase in ECM density,
composed of unorganized collagens (I, III, IV and V) and proteoglycans (biglycan, fibromodulin, perlecan and versican). The
desmoplastic collagen fibers were thick, with an altered orientation, as well as deposited as bundles. This increased ECM
density inhibited the migration and invasion of the colorectal tumor cells in both 2D and 3D co-culture systems. Therefore
this study sheds light on a possible restricting role desmoplasia could play in colorectal cancer invasion. 相似文献
45.
46.
Susan A. Novotny Tara L. Mader Angela G. Greising Angela S. Lin Robert E. Guldberg Gordon L. Warren Dawn A. Lowe 《PloS one》2014,9(8)
The objective of the study was to determine if low intensity, high frequency vibration training impacted the musculoskeletal system in a mouse model of Duchenne muscular dystrophy, relative to healthy mice. Three-week old wildtype (n = 26) and mdx mice (n = 22) were randomized to non-vibrated or vibrated (45 Hz and 0.6 g, 15 min/d, 5 d/wk) groups. In
vivo and ex
vivo contractile function of the anterior crural and extensor digitorum longus muscles, respectively, were assessed following 8 wks of vibration. Mdx mice were injected 5 and 1 days prior to sacrifice with Calcein and Xylenol, respectively. Muscles were prepared for histological and triglyceride analyses and subcutaneous and visceral fat pads were excised and weighed. Tibial bones were dissected and analyzed by micro-computed tomography for trabecular morphometry at the metaphysis, and cortical geometry and density at the mid-diaphysis. Three-point bending tests were used to assess cortical bone mechanical properties and a subset of tibiae was processed for dynamic histomorphometry. Vibration training for 8 wks did not alter trabecular morphometry, dynamic histomorphometry, cortical geometry, or mechanical properties (P≥0.34). Vibration did not alter any measure of muscle contractile function (P≥0.12); however the preservation of muscle function and morphology in mdx mice indicates vibration is not deleterious to muscle lacking dystrophin. Vibrated mice had smaller subcutaneous fat pads (P = 0.03) and higher intramuscular triglyceride concentrations (P = 0.03). These data suggest that vibration training at 45 Hz and 0.6 g did not significantly impact the tibial bone and the surrounding musculature, but may influence fat distribution in mice. 相似文献
47.
Matthias Oelze Swenja Kr?ller-Sch?n Philipp Welschof Thomas Jansen Michael Hausding Yuliya Mikhed Paul Stamm Michael Mader Elena Zin?ius Saule Agdauletova Anna Gottschlich Sebastian Steven Eberhard Schulz Serge P. Bottari Eric Mayoux Thomas Münzel Andreas Daiber 《PloS one》2014,9(11)
Objective
In diabetes, vascular dysfunction is characterized by impaired endothelial function due to increased oxidative stress. Empagliflozin, as a selective sodium-glucose co-transporter 2 inhibitor (SGLT2i), offers a novel approach for the treatment of type 2 diabetes by enhancing urinary glucose excretion. The aim of the present study was to test whether treatment with empagliflozin improves endothelial dysfunction in type I diabetic rats via reduction of glucotoxicity and associated vascular oxidative stress.Methods
Type I diabetes in Wistar rats was induced by an intravenous injection of streptozotocin (60 mg/kg). One week after injection empagliflozin (10 and 30 mg/kg/d) was administered via drinking water for 7 weeks. Vascular function was assessed by isometric tension recording, oxidative stress parameters by chemiluminescence and fluorescence techniques, protein expression by Western blot, mRNA expression by RT-PCR, and islet function by insulin ELISA in serum and immunohistochemical staining of pancreatic tissue. Advanced glycation end products (AGE) signaling was assessed by dot blot analysis and mRNA expression of the AGE-receptor (RAGE).Results
Treatment with empagliflozin reduced blood glucose levels, normalized endothelial function (aortic rings) and reduced oxidative stress in aortic vessels (dihydroethidium staining) and in blood (phorbol ester/zymosan A-stimulated chemiluminescence) of diabetic rats. Additionally, the pro-inflammatory phenotype and glucotoxicity (AGE/RAGE signaling) in diabetic animals was reversed by SGLT2i therapy.Conclusions
Empagliflozin improves hyperglycemia and prevents the development of endothelial dysfunction, reduces oxidative stress and improves the metabolic situation in type 1 diabetic rats. These preclinical observations illustrate the therapeutic potential of this new class of antidiabetic drugs. 相似文献48.
In the present study, unilamellar liposomes coated with the crystalline bacterial cell surface layer (S-layer) protein of Bacillus stearothermophilus PV72/p2 were used as matrix for defined binding of functional molecules via the avidin- or streptavidin-biotin bridge. The liposomes were composed of dipalmitoyl phosphatidylcholine, cholesterol and hexadecylamine in a molar ratio of 10:5:4 and they had an average size of 180 nm. For introducing specific functions into the S-layer lattice without affecting substances encapsulated within the liposomes, crosslinking and activation reagents had to be identified which did not penetrate the liposomal membrane. Among different reagents, a hydrophilic dialdehyde generated by periodate cleavage of raffinose and a sulfo-succinimide activated dicarboxylic acid were found to be impermeable for the liposomal membrane. Both reagents completely crosslinked the S-layer lattice without interfering with its regular structure. Biotinylation of S-layer-coated liposomes was achieved by coupling p-diazobenzoyl biocytin which preferably reacts with the phenolic residue of tyrosine or with the imidazole ring of histidine. By applying this method, two biotin residues accessible for subsequent avidin binding were introduced per S-layer subunit. As visualized by labeling with biotinylated ferritin, an ordered monomolecular layer of streptavidin was formed on the surface of the S-layer-coated liposomes. As a second model system, biotinylated anti-human IgG was attached via the streptavidin bridge to the biotinylated S-layer-coated liposomes. The biological activity of the bound anti-human IgG was confirmed by ELISA. 相似文献
49.
Elke EM Brouwers Alwin DR Huitema Jos H Beijnen Jan HM Schellens 《BMC clinical pharmacology》2008,8(1):7
Background
The aim of this study was to evaluate long-term platinum retention in patients treated with cisplatin and oxaliplatin. 相似文献50.
A Gualberto D LePage G Pons S L Mader K Park M L Atchison K Walsh 《Molecular and cellular biology》1992,12(9):4209-4214