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271.
Laila Abdel moteleb Selim Dina Ahmed Mehaney Fayza Abdel Hamid Hassan Sawsan Abdel Hady Hassan Iman Gamaleldin Randa Sabry Enrico Bertini 《Journal of Genetic Engineering and Biotechnology》2013,11(1):61-68
Congenital muscular dystrophies (CMD) are a group of heterogeneous inherited autosomal recessive disorders characterized by muscular weakness, hypotonia and contractures. The Merosin Negative CMD (MNCMD) is considered to be the most severe form and is usually associated with white matter abnormalities as seen with brain imaging. Merosin is also expressed in the nervous system and its deficiency could affect its development. This article describes the clinical picture, muscle biopsy findings and neuroimaging abnormalities of eight Egyptian Pediatric patients with the clinical presentation of merosin negative congenital muscular dystrophy. The leading clinical presentation in almost all patients was severe hypotonia, muscular weakness and failure to achieve motor developmental milestones, only Case 2 walked at 2 years of age. Mentality was normal in most patients with exception of Case 2 in whom scholastic achievement was poor and was associated with behavior abnormality. Serum Creatine kinase ranged from moderate to severe elevation, 536–3563 U/L, Electromyography demonstrated a myopathic pattern in all patients. Brain MRI showed extensive demyelination of the cerebral white matter in 6/8 patients with extension to cerebellar demyelination in Case 5. 5/8 patients underwent muscle biopsy for which immunofluorescence staining for merosin demonstrated complete deficiency of laminin α2 in Case 5 & partial deficiency of laminin α2 in Case 2.This report demonstrates the utility of Immunofluorescence staining as a guide to confirm the diagnosis of MDCMD especially when molecular diagnosis is not available. 相似文献
272.
Salib JY Daniel EN Hifnawy MS Azzam SM Shaheed IB Abdel-Latif SM 《Zeitschrift für Naturforschung. C, Journal of biosciences》2011,66(9-10):453-459
Graded concentrations (0.1-100 mg/mL reaction mixture) of the methanolic extract of the flowers of Hibiscus rosa-sinensis Linn., its water-soluble fraction as well as compounds isolated from this fraction were tested for their inhibitory effect on alkaline phosphatase enzyme activity in vitro. Both the methanolic extract and its water-soluble fraction showed significant inhibitory effects on the enzyme activity in vitro. On screening the activity of the compounds isolated from the water-soluble fraction, its high inhibitory activity was attributed to the presence of quercetin-7-O-galactoside which showed a high potent inhibition of the enzyme activity reaching 100% at 100 mg/mL reaction mixture. Phytochemical investigations of the water-soluble fraction were also carried out and afforded ten polyphenolic compounds including two new natural compounds, namely kaempferol-7-O-[6'-O-p-hydroxybenzoyl-beta-D-glucosyl-(1-->6)-beta-D-glucopyranoside] and scutellarein-6-O-alpha-L-rhamnopyranoside-8-C-beta-D-glucopyranoside). The chemical structure of the isolated compounds was elucidated on the basis of chemical and spectral data. 相似文献
273.
Moussa IA Banister SD Giboureau N Meikle SR Kassiou M 《Bioorganic & medicinal chemistry letters》2011,21(22):6820-6823
N-(2-Benzofuranylmethyl)-N'-[4-(2-fluoroethoxy)benzyl]piperazine (6, σ(1)K(i)=2.6 nM) was radiolabeled with fluorine-18 to provide a potential σ(1) receptor radioligand for use in positron emission tomography (PET). Radiofluorination of the appropriate tosylate precursor furnished [(18)F]6 with a specific activity of 45 GBq/μmol, in an average radiochemical yield of 18% and greater than 98% radiochemical purity. MicroPET imaging in Papio hamadryas baboon brain revealed [(18)F]6 uptake consistent with σ receptor distribution, and specificity for σ receptors was demonstrated in a haloperidol pre-treated animal. [(18)F]6 possesses suitable properties for PET imaging of σ(1) receptors, and further investigation of this σ(1) receptor tracer is warranted. 相似文献
274.
Moussa IA Banister SD Akladios FN Chua SW Kassiou M 《Bioorganic & medicinal chemistry letters》2011,21(19):5707-5710
In our continued exploration of disubstituted piperazine derivatives as sigma (σ) receptor ligands with central nervous system (CNS) activity, a series of N-(2-benzofuranylmethyl)-N'-(methoxyphenylalkyl)piperazines (16-21 and 26-31) were synthesized, anticipating that these ligands would better suit the structural requirements of the current σ(1) pharmacophore. Affinities of these ligands for σ(1) and σ(2) receptors were investigated by means of radioligand binding assays, with the identification of N-(2-benzofuranylmethyl)-N'-[3-(4-methoxyphenyl)propyl]piperazine (29, K(i)=3.1 nM, σ(2)/σ(1)=45) as a selective σ(1) ligand. The σ(1) affinities and subtype selectivities of piperazines 16-21 and 26-31 were generally comparable to the corresponding benzylic analogs. Additionally, the affinities of 16-21 and 26-31 for the 5-HT(2B) receptor were much lower than the relatively nonselective methoxybenzylic analogs 2-4, indicating that elongation of the alkyl tether generally improved selectivity for σ(1) receptors. 相似文献
275.
Banister SD Moussa IA Beinat C Reynolds AJ Schiavini P Jorgensen WT Kassiou M 《Bioorganic & medicinal chemistry letters》2011,21(1):38-41
In our continued exploration of trishomocubane derivatives with central nervous system (CNS) activity, N-arylalkyl-8-aminopentacyclo[5.4.0.02,6.03,10.05,9]undecanes (10-13) displaying affinity for the sigma (σ) receptor were also found, in several cases, to interact with the dopamine transporter (DAT). Compound 12 was identified as the first trishomocubane-derived high affinity DAT ligand (Ki = 1.2 nM), with greater than 8300-fold selectivity over the monoamine transporters NET and SERT, and only low to moderate affinity for σ1 and σ2 receptors. 相似文献
276.
Banister SD Moussa IA Jorgensen WT Chua SW Kassiou M 《Bioorganic & medicinal chemistry letters》2011,21(12):3622-3626
A series of N-substituted 4-azahexacyclo[5.4.1.02,6.03,10.05,9.08,11]dodecan-3-ols incorporating the respective arylalkyl subunits from several known sigma (σ) receptor ligands were synthesized and evaluated for their affinity against σ receptors and dopamine receptors. The hybrid trishomocubane-derived ligands (4-6) showed good selectivity for σ1 and σ2 receptors over multiple dopamine receptors. The molecular hybrid obtained from haloperidol and 4-azahexacyclo[5.4.1.02,6.03,10.05,9.08,11]dodecan-3-ol (4, σ1Ki = 27 nM, σ2Ki = 55 nM) showed reduced affinity for D1-D5 dopamine receptors when compared to haloperidol itself. The compound with the greatest σ1 affinity in the series, benzamide 4 (σ1Ki = 7.6 nM, σ2Ki = 225 nM) showed a complete reversal of the subtype selectivity displayed by the highly σ2 selective parent benzamide, RHM-2 (3, σ1Ki = 10412 nM, σ2Ki = 13.3 nM). 相似文献
277.
Hydroxyzine HCl is used in oral formulations for the treatment of urticaria and atopic dermatitis. Dizziness, blurred vision,
and anticholinergic responses, represent the most common side effects. It has been shown that controlled release of the drug
from a delivery system to the skin could reduce the side effects while reducing percutaneous absorption. Therefore, the aim
of the present study was to produce an effective drug-loaded dosage form that is able to control the release of hydroxyzine
hydrochloride into the skin. The Microsponge Delivery System is a unique technology for the controlled release of topical
agents, and it consists of porous polymeric microspheres, typically 10–50 μm in diameter, loaded with active agents. Eudragit
RS-100 microsponges of the drug were prepared by the oil in an oil emulsion solvent diffusion method using acetone as dispersing
solvent and liquid paraffin as the continuous medium. Magnesium stearate was added to the dispersed phase to prevent flocculation
of Eudragit RS-100 microsponges. Pore inducers such as sucrose and pregelatinized starch were used to enhance the rate of
drug release. Microsponges of nearly 98% encapsulation efficiency and 60–70% porosity were produced. The pharmacodynamic effect
of the chosen preparation was tested on the shaved back of histamine-sensitized rabbits. Histopathological studies were driven
for the detection of the healing of inflamed tissues. 相似文献
278.
Nicolas Baeyens Iman Latrache Xavier Yerna Gauthier Noppe Sandrine Horman Nicole Morel 《Biochemical and biophysical research communications》2013
Ezrin, radixin, and moesin possess a very similar structure with a C-terminal actin-binding domain and a N-terminal FERM interacting domain. They are known to be involved in cytoskeleton organization in several cell types but their function in vascular smooth muscle cells (VSMC) is still unknown. The aim of this study was to investigate the role of ERM proteins in cell migration induced by PDGF, a growth factor involved in pathophysiological processes like angiogenesis or atherosclerosis. We used primary cultured VSMC obtained from rat aorta, which express the three ERM proteins. Simultaneous depletion of the three ERM proteins with specific siRNAs abolished the effects of PDGF on cell architecture and migration and markedly increased cell adhesion and focal adhesion size, while these parameters were only slightly affected by depletion of ezrin, radixin or moesin alone. Rac1 activation, cell proliferation, and Ca2+ signal in response to PDGF were unaffected by ERM depletion. These results indicate that ERM proteins exert a redundant control on PDGF-induced VSMC migration by regulating focal adhesion turn-over and cell adhesion to substrate. 相似文献
279.
Gamaleldin I. Harisa 《Journal of biochemical and molecular toxicology》2013,27(8):398-405
The objective of the present study was to assess superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), paraoxonase (PON1), glutathione reductase (GR), and catalase (CAT) activities ratio and their relationship with DNA oxidative damage in rats treated with cisplatin (3 mg/kg bwt/day) in the presence and absence of benfotiamine (100 mg/kg/day) for 25 days. Cisplatin‐induced renal damage was evidenced by renal dysfunction and elevated oxidative stress markers. SOD activity and levels of nitric oxide, protein carbonyl, malondialdehyde, and 8‐hydroxy‐2'‐deoxyguanosine were significantly increased by cisplatin treatment. Moreover, the ratios of GPx/GR, SOD/GPx, SOD/CAT, and SOD/PON1 were significantly increased compared to control. In contrast, glutathione levels were significantly decreased by cisplatin treatment. Simultaneous treatment of rats with cisplatin and benfotiamine ameliorate these variables to values near to those of control rats. This study suggests that benfotiamine can prevent cisplatin‐induced nephrotoxicity by inhibiting formation reactive species of oxygen and nitrogen. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:398‐405, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21501 相似文献
280.
Pseudoidium javanicum is proposed as a new species based on analyses of 28S, ITS and IGS rDNA sequences, and morphological data. This new species was found on Acalypha wilkesiana var. marginata, A. argentea, and A. cristata collected from Cibodas Botanical Garden, Bogor (West Java Province, Indonesia). Our analyses showed that all these specimens have identical rDNA sequences and similar morphological characteristics. They form a distinct clade separated from other species of Erysiphaceae. Pseudoidium javanicum differs from Erysiphe acalyphae by having shorter conidiophores and foot cells 1–3 times as long as the 0–2 following cells. The conidial size of Ps. javanicum is also smaller than that of E. jatrophae. 相似文献