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81.
Francesco Brigo Pasquale Striano Ganna Balagura 《Expert opinion on emerging drugs》2013,18(4):261-269
ABSTRACTIntroduction: Dravet syndrome (DS) is an early-onset genetic developmental epileptic encephalopathy characterized by multiple seizure types which are refractory to antiseizure medication. There is an unmet need for effective and tolerable drugs to control different seizure types in DS types, with the aim of improving quality of life and preventing neurological impairment.Areas covered: Narrative review of efficacy and tolerability of fenfluramine, cannabidiol (CBD), verapamil, and modulators of serotonin signaling pathways (lorcaserin or trazodone) in the treatment of DS.Expert opinion/commentary: A recent large randomized controlled trial has shown that CBD is effective in the treatment of DS; preliminary data from the placebo-controlled trial on fenfluramine are also promising. Further studies are definitely required to evaluate the role of verapamil and modulators of serotonin signaling in DS. At present, drugs used to treat seizures in DS treat the symptoms of epilepsy rather than its cause(s). Future research should focus on elucidating the natural history of DS and whether appropriate treatment can have a beneficial impact on its disease course. A multidisciplinary, individualized approach to care of DS patients is required. 相似文献
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Abstract Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays a critical role in the regulation of basic cellular functions, including cellular growth and proliferation. In this study we describe the generation and characterization of novel monoclonal antibodies directed against mTOR protein kinase. A GST-tagged fragment of mTOR expressed in bacteria was used as an antigen. Antibody-producing hybridoma cells were obtained by fusing SP2/0 myeloma cells with splenocytes from immunized mice. Anti-mTOR antibody-producing hybridoma cell lines were first identified by enzyme-linked immunosorbent assay and then subcloned by limiting dilution. Antibodies produced by selected clones were further tested for their reactivity towards the GST/mTOR 1334-1504 recombinant protein. Furthermore, antibody produced by F11 clone was shown to recognize specifically mTOR in different tissues and cell lines in Western blotting, immunoprecipitation, and immunohistochemistry. In addition, mTOR F11 antibody was suitable for immunoprecipitating and testing mTOR activity in in vitro kinase assay. In summary, generated antibodies will be useful for investigating mTOR signaling complexes in normal and pathological states. 相似文献
84.
Ganna Livshyts Svetlana Podlesnaja Sergey Kravchenko Iryna Sudoma Ludmila Livshits 《Journal of assisted reproduction and genetics》2009,26(1):29-34
Purpose To evaluate the association between phenotype and follicle stimulating hormone receptor (FSHR) genotype in women with ovarian
dysfunction and patients with “poor response” to gonadotropin stimulation of ovulation.
Methods FSHR gene SNPs were analyzed by PCR and RFLP. “Poor responders” (ovarian dysfunction) group and “good responders” group constituted
the study group. Normo-ovulatory women who gave birth to naturally conceived children formed control groups: under 35 years
of age (control I) and over 35 years of age (control II).
Results The frequency of Ala307-Ser680/Ala307-Ser680 genotype was significantly more prevalent in the ovarian dysfunction group (26%)
compared to the control I (7.7%) (P < 0.001) and a “good responders” group (12.5%) (P < 0.05); and in a “poor responders” group (33.3%) compared to a “good responders” group (P < 0.05), control I (P < 0.001) and control II (17.5%) (P < 0.05).
Conclusions Our data shows the prevalence of the Ala307-Ser680/ Ala307-Ser680 genotype in the both groups of patients. The finding should
have impact on the delineation of stimulation protocols.
FSHR receptor gene polymorphisms and diminished ovarian reserve.
Capsule The association between phenotype and Asn680Ser and Thr307Ala FSHR gene polymorphisms was found in women with ovarian dysfunction
and poor response to FSH ovarian stimulation. 相似文献
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86.
Prostate cancer is the most commonly diagnosed cancer and second most common cause of cancer deaths in American men. Its long latency, slow progression, and high incidence rate make prostate cancer ideal for targeted chemopreventative therapies. Therefore, chemoprevention studies and clinical trials are essential for reducing the burden of prostate cancer on society. Epidemiological studies suggest that tea consumption has protective effects against a variety of human cancers, including that of the prostate. Laboratory and clinical studies have demonstrated that green tea components, specifically the green tea catechin (GTC) epigallocatechin gallate, can induce apoptosis, suppress progression, and inhibit invasion and metastasis of prostate cancer. Multiple mechanisms are involved in the chemoprevention of prostate cancer with GTCs; understanding and refining models of fundamental molecular pathways by which GTCs modulate prostate carcinogenesis is essential to apply the utilization of green tea for the chemoprevention of prostate cancer in clinical settings. The objective of this article is to review and summarize the most current literature focusing on the major mechanisms of GTC chemopreventative action on prostate cancer from laboratory, in vitro, and in vivo studies, and clinical chemoprevention trials. 相似文献
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Eugene V. Grishin Ganna A. Savchenko Alexander A. Vassilevski Yuliya V. Korolkova Yaroslav A. Boychuk Viacheslav Y. Viatchenko‐Karpinski Kirill D. Nadezhdin Alexander S. Arseniev Kirill A. Pluzhnikov Vyacheslav B. Kulyk Nana V. Voitenko Oleg O. Krishtal 《Annals of neurology》2010,67(5):680-683
P2X3 purinoreceptors expressed in mammalian sensory neurons play a key role in several processes, including pain perception. From the venom of the Central Asian spider Geolycosa sp., we have isolated a novel peptide, named purotoxin‐1 (PT1), which is to our knowledge the first natural molecule exerting powerful and selective inhibitory action on P2X3 receptors. PT1 dramatically slows down the removal of desensitization of these receptors. The peptide demonstrates potent antinociceptive properties in animal models of inflammatory pain. ANN NEUROL 2010;67:680–683 相似文献
89.
Martínez Mdel P Bozzini C Olivera MI Dmytrenko G Conti MI 《Journal of bone and mineral metabolism》2011,29(5):526-534
Aluminum (Al) is an element to which humans are widely exposed. Chronic administration induces a negative effect on bone tissue,
affecting collagen synthesis and matrix mineralization. Its toxic effects are cumulative. Hypobaric hypoxia induces stress
erythropoiesis, leading to hypertrophy of the erythropoietic marrow affecting the bone. This study was designed to evaluate
the risk of Al bone toxicity among immature rats maintained at simulated high altitude (SHA) by mechanical assessment of stiffness
and strength, calculation of some indicators of bone material and geometrical properties, as well as blood determinations.
Forty growing rats were divided into control and experimental groups whether injected with vehicle or Al, as Al(OH)3, three times a week for 3 months. Half of each group was exposed to hypobaric conditions (HX) by placing the animals in a
SHA chamber. Both treatments negatively affected structural properties of bones, decreasing the maximum capacity to withstand
load, the limit elastic load and the capacity of absorbing energy in elastic conditions. Al administration significantly depressed
mandible structural stiffness, although diaphyseal stiffness was not modified. Indicators of bone material intrinsic properties,
elastic modulus and stress, were significantly reduced by Al or HX. Treatments increased the diaphyseal sectional bending
moment of inertia, suggesting that femur, but not mandible, compensates for the decline in the material properties with an
adaptation of its architecture to maintain structural properties. The different biomechanical behaviors between the two kinds
of bone are probably due to their different embryological origin and specific functions, as mandible is a bone that adjusts
its strength to biting forces, whereas femur is designed to support load. 相似文献
90.
Szabo S Deng X Tolstanova G Khomenko T Paunovic B Chen L Jadus M Sandor Z 《Current pharmaceutical design》2011,17(16):1633-1642
Gastrointestinal (GI) ulcers are essentially internal wounds that resist normal healing processes. Since their pathogenesis is poorly understood, and the etiologic (e.g., gastric acid, aspirin-like drugs, stress) and aggravating factors (e.g., H. pylori) are not well characterized, the remaining therapeutic option is to accelerate healing. Superficial mucosal lesions, i.e., erosions usually heal by epithelial regeneration and restitution, but when ulcers involve the muscularis propria, smooth muscle cells do not divide/regenerate. These deep lesions are filled by granulation tissue, i.e., angiogenesis followed by proliferation of connective tissue fibroblasts that deposit collagen over which adjacent surviving and dividing epithelial cells migrate to complete the healing. Our laboratory was the first to postulate that stimulation of angiogenesis alone might be sufficient to accelerate ulcer healing in the GI tract. Indeed, daily treatment of rats with bFGF, PDGF or VEGF markedly improved the healing of cysteamine-induced chronic duodenal ulcers, without any reduction in gastric acid secretion. These results were reproduced by a single dose of gene therapy by adenoviral vectors encoding PDGF or VEGF genes. The molar potency of angiogenic growth factors was 2-7 million times better than the antiulcerogenic effect of antisecretory H2 antagonists. Since histologically & pathologically gastroduodenal ulcers look similar to ulcers in the lower GI tract, we also predicted that the healing of experimental ulcerative colitis might be also improved by these angiogenic growth factors. Rectal enemas containing bFGF or PDGF indeed accelerated the healing of chemically induced ulcerative colitis in rats. VEGF, also known as VPF (vascular permeability factor), however, had no effect or slightly aggravated the colonic lesions. Injection of anti-VEGF neutralizing antibodies, however, counteracted the increased vascular permeability in the early stages of experimental ulcerative colitis and subsequently decreased the number of inflammatory cells in colonic ulcers in rats, resulting in significantly improved healing in the lower GI tract lesions. Thus, the three angiogenic growth factors tested exerted beneficial effect on gastroduodenal ulcers, and rectal enemas with bFGF or PDGF also accelerated the healing of experimental ulcerative colitis. Surprisingly, we achieved the latter effect with anti-VEGF antibodies, most likely because of the pro-inflammatory actions of VEGF in the pathogenesis of ulcerative colitis. 相似文献