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81.
Marina Romozzi Guido Primiano Eleonora Rollo Lorena Travaglini Paolo Calabresi Serenella Servidei Catello Vollono 《The journal of headache and pain》2021,22(1)
Background and aimsHemiplegic migraine (HM) is a rare form of migraine characterized by the presence of a motor and other types of aura. HM can be sporadic or familial. Familial hemiplegic migraine (FHM) is an autosomal dominant disorder, classified into 3 subtypes, based on the gene involved (CACNA1A in FHM1, ATP1A2 in FHM2 and SCN1A in FHM3). The clinical presentation is highly heterogeneous and some attacks may be severe.We report the clinical characteristics and genetic analysis of 12 patients belonging to a family with CACNA1A-p.Thr501Met gene mutation.MethodsWe screened for mutations in CACNA1A gene 15 patients belonging to the same family. The exonic sequences of CACNA1A were analyzed using a Tru-seq® Custom Amplicon (TSCA) (Illumina Inc., San Diego, CA) targeted capture and paired end library kit. Sanger sequencing was used to confirm CACNA1A variants and segregation analysis.ResultsCACNA1A-p.Thr501Met mutation was found in 12 of the 15 patients screened, which was compatible with the diagnosis of FHM1.Attacks of hemiplegic migraine were reported by 10 of the 12 subjects (83.33%). Only one subject developed persistent mild cerebellar symptoms and none of the subjects developed cerebellar atrophy.DiscussionThe variant p.Thr501Met was described previously in association with episodic ataxia and rarely with FHM related to cerebellar symptoms. FHM1 has a broad clinical spectrum and about half of the families have cerebellar involvement. In our study, only one patient developed persistent cerebellar deficits.These data suggest that CACNA1A-p.Thr501Met mutation can occur prevalently as hemiplegic migraine.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01297-5. 相似文献
82.
Yoshitake Matsumoto Hitoshi Okamura Yukio Ichitani Noboru Yanaihara Teruo Nakajima Yasuhiko Ibata 《Brain research bulletin》1992,28(5)
It has already been demonstrated that chronic treatment with the dopamine receptor blocker, haloperidol, results in an increase of proenkephalin-A-derived peptides in the caudate-putamen (CP). To examine this phenomenon at the cellular level, we used immunocytochemistry to investigate the effects of haloperidol on [Met]enkephalin-Arg6-Gly7-Leu8 (MEAGL) immunoreactivity in the rat forebrain. After daily haloperidol (5 mg/kg, IP, for 6 days) or haloperidol decanoate (70 mg/kg, IM, given once or twice) treatment, immunoreactive neurons appeared diffusely in the whole CP and in the core part of the nucleus accumbens (Acb) and less frequently in the outer shell part of the Acb and the cell-dense layer of the tuberculum olfactorium (TuO). Increase of MEAGL-immunoreactive fibers in the CP, Acb and TuO was also detected after these treatments, a particularly prominent increase being found in the striopallidal terminals in the globus pallidus and ventral pallidum. Haloperidol or haloperidol decanoate had no effect on MEAGL immunoreactivity in the cerebral cortex, amygdala, or hypothalamus. Reserpine treatment (5 mg/kg, IP, for 6 days) caused similar effects on the dorsal and ventral striopallidal system and the direct injection of 6-hydroxydopamine (10 μ/5 μl) into the CP led to the appearance of MEAGL-immunoreactive neurons in accordance with the depleted dopaminergic terminal area. These findings suggest that haloperidol influences enkephalinergic neurons region specifically and that in the dorsal and ventral striopallidal enkephalinergic system haloperidol increases MEAGL immunoreactivity in cell bodies, fibers and terminals by blocking intrastriatal dopaminergic neurotransmission. 相似文献
83.
84.
周丽娜 《浙江中西医结合杂志》2019,29(6)
目的 探讨体外联用青蒿琥酯对顺铂抗前列腺癌活性的影响并研究其机制。方法: 前列腺癌细胞系LNCaP的细胞活力抑制率用噻唑蓝(MTT)法进行检测。LNCaP细胞的凋亡用流式细胞术进行检测。LNCaP细胞中Met的表达水平,AKT和Bad的磷酸化水平,caspase-9和caspase-3的活化水平用western blot实验进行检测。Bad与Bcl-xl及Bcl-2的相互作用用免疫共沉淀法进行检测。结果: 青蒿琥酯联合顺铂组LNCaP的细胞活力抑制率(61.4±4.9)%和凋亡率(34.8±2.9)%均显著高于顺铂单处理组的细胞活力抑制率(14.7±1.1)%(P<0.05)和凋亡率(12.5±1.0)%(P<0.05)。青蒿琥酯联合顺铂组LNCaP细胞的Met表达水平,AKT和Bad的磷酸化水平均低于顺铂组,而青蒿琥酯联合顺铂组LNCaP细胞的Bad与Bcl-xl及Bcl-2的结合水平,caspase-9和caspase-3的活化水平均均高于顺铂组。青蒿琥酯发挥对顺铂的辅助治疗作用依赖于Met的抑制,青蒿琥酯+顺铂+Met质粒组LNCaP的细胞活力抑制率(20.3±1.4)%和凋亡率(15.5±1.2)%均显著低于顺铂+顺铂组的细胞活力抑制率(61.4±4.9)%(P<0.05)和凋亡率(34.8±2.9)%(P<0.05)。结论: 青蒿琥酯通过Met/AKT/Bad途径增强顺铂对前列腺癌细胞的杀伤活性。 相似文献
85.
Katherine Bergwerk Rena E. Falk Ben J. Glasgow Yaron S. Rabinowitz 《Ophthalmic genetics》2013,34(1):17-20
Purpose: To illustrate a good visual outcome following penetrating keratoplasty in a patient with Sly disease, a rare mucopolysaccharidosis (MPS) caused by a deficiency of ß-glucuronidase. Methods: A 15-year-old male with progressive bilateral corneal opacification had a complete medical, genetic, and ophthalmic evaluation followed by a penetrating keratoplasty. Results: The cornea has remained clear for two years following surgery. Histopathology of the corneal button demonstrated vacuoles and granular inclusions consistent with this lysosomal storage disease. Conclusion: While research is ongoing in the fields of enzyme replacement and bone marrow transplantation, these treatments may not alleviate or reverse the corneal clouding. This case illustrates that cornea transplantation may be a valuable treatment option for visually rehabilitating such patients. 相似文献
86.
Jennifer K. McCleese Misty D. Bear Stacey L. Fossey Robert M. Mihalek Kevin P. Foley Weiwen Ying James Barsoum Cheryl A. London 《International journal of cancer. Journal international du cancer》2009,125(12):2792-2801
Osteosarcoma (OSA), the most common malignant bone tumor in dogs and children, exhibits a similar clinical presentation and molecular biology in both species. Unfortunately, 30–40% of children and 90% of dogs still die of disease despite aggressive therapy. The purpose of this study was to test the biologic activity of a novel heat shock protein 90 (HSP90) inhibitor, STA‐1474, against OSA. Canine and human OSA cell lines and normal canine osteoblasts were treated with STA‐1474 and evaluated for effects on proliferation (CyQuant), apoptosis (Annexin V, PARP cleavage, caspase 3/7 activation) and known HSP90 client proteins. HSP90 was immunoprecipitated from normal and malignant osteoblasts and Western blotting for co‐chaperones was performed. Mice bearing canine OSA xenografts were treated with STA‐1474, and tumors samples were evaluated for caspase‐3 activation and loss of p‐Akt/Akt. Treatment with STA‐1474 promoted loss of cell viability, inhibition of cell proliferation and induction of apoptosis in OSA cell lines. STA‐1474 and its active metabolite STA‐9090 also demonstrated increased potency compared to 17‐AAG. STA‐1474 exhibited selectivity for OSA cells versus normal canine osteoblasts, and HSP90 co‐precipitated with co‐chaperones p23 and Hop in canine OSA cells but not in normal canine osteoblasts. Furthermore, STA‐1474 downregulated the expression of p‐Met/Met, p‐Akt/Akt and p‐STAT3. Finally, STA‐1474 induced tumor regression, caspase‐3 activation and downregulation of p‐Met/Met and p‐Akt/Akt in OSA xenografts. Together, these data suggest that HSP90 represents a relevant target for therapeutic intervention in OSA. © 2009 UICC 相似文献
87.
Effect of functional catechol-O-methyltransferase Val158Met polymorphism on physical aggression 总被引:1,自引:0,他引:1
M. A. Kulikova N. V. Maluchenko M. A. Timofeeva V. A. Shlepzova J. V. Schegolkova O. V. Sysoeva A. M. Ivanitsky A. G. Tonevitsky 《Bulletin of experimental biology and medicine》2008,145(1):62-64
Genetic and psychological analysis of the relationships between catechol-O-methyltransferase Val158Met polymorphism and various
types of aggressiveness was performed in 114 women. Dispersion analysis revealed significant association of ValVal genotype
with elevated physical aggression.
__________
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 1, pp. 68–70, January, 2008 相似文献
88.
目的通过建立大鼠静脉自体静脉移植模型,应用甲硫氨酸脑啡肽(M—Enk)及其长效受体拮抗剂盐酸纳曲酮(NTX)观察M—Enk对内膜增殖的影响,并初步揭示其中的作用机制。方法建立M—Enk、NTX及对照组三组大鼠自体静脉移植模型,并分别给药;于不同时期取移植静脉标本,做形态学观察、c—fos、c—myc免疫组化染色、Western blot半定量检测,最后对数据采用方差分析及q检验。结果1.M—Enk组内膜厚度各时段较对照组明显降低,NTX组内膜厚度各时段较对照组明显增加;2.M—Enk组移植1~3天c—fos蛋白表达较对照组明显受到抑制,NTX组移植1~3天c—fos蛋白表达较对照组明显升高;3.M—Enk组移植1~2周c—myc蛋白表达较对照组明显受到抑制,NTX组移植后3天至2周,c—myc蛋白表达较对照组明显升高;4.Western blot结果与免疫组化结果基本相符。结论血管移植后,创伤破坏了内源性M—Enk与其受体结合的自分泌环,诱发了c—fos、c—myc等早反应基因的表达,从而引起更多的迟反应基因的表达,最终形成血管内膜的增生。 相似文献
89.
《European psychiatry》2014,29(5):293-300
PurposeTo test whether firstly, different parental rearing components were associated with different dimensions of psychiatric symptoms in adulthood, secondly BDNF-Val66Met polymorphism moderated this association and thirdly, this association was due to genetic confounding.MethodPerceived parental rearing according to Parental Bonding Instrument (PBI), psychiatric symptoms evaluated with the Brief Symptom Inventory (BSI) and the BDNF-Val66Met polymorphism were analyzed in a sample of 232 adult twins from the general population.ResultsIn the whole sample, paternal care was negatively associated with depression. Maternal overprotection was positively associated with paranoid ideation, obsession-compulsion and somatization. Gene-environment interaction effects were detected between the BDNF-Val66Met polymorphism and maternal care on phobic anxiety, paternal care on hostility, maternal overprotection on somatization and paternal overprotection also in somatization. In the subsample of MZ twins, intrapair differences in maternal care were associated with anxiety, paranoid ideation and somatization.ConclusionsMet carriers were, in general, more sensitive to the effects of parental rearing compared to Val/Val carriers in relation to anxiety and somatization. Contra-intuitively, our findings suggest that high rates of maternal care might be of risk for Met carriers regarding anxiety. Results from analyses controlling for genetic confounding were in line with this finding. 相似文献
90.
Hayley Nehoff Neha N. Parayath Melanie J. McConnell Sebastien Taurin Khaled Greish 《Oncotarget》2015,6(35):37948-37964
Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. Despite the advances in surgery, radiotherapy and chemotherapy, patient survival averages only 14.6 months. In most GBM tumors, tyrosine kinases show increased activity and/or expression and actively contribute to the development, recurrence and onset of treatment resistance; making their inhibition an appealing therapeutic strategy. We compared the cytotoxicity of 12 tyrosine kinase inhibitors in vitro. A combination of crizotinib and dasatinib emerged as the most cytotoxic across established and primary human GBM cell lines. The combination treatment induced apoptotic cell death and polyploidy. Furthermore, the combination treatment led to the altered expression and localization of several tyrosine kinase receptors such as Met and EGFR and downstream effectors as such as SRC. Furthermore, the combination treatment reduced the migration and invasion of GBM cells and prevented endothelial cell tube formation in vitro. Overall, our study demonstrated the broad specificity of a combination of crizotinib and dasatinib across multiple GBM cell lines. These findings provide insight into the development of alternative therapy for the treatment of GBM. 相似文献