全文获取类型
收费全文 | 163篇 |
免费 | 8篇 |
国内免费 | 4篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 2篇 |
基础医学 | 28篇 |
临床医学 | 6篇 |
内科学 | 3篇 |
皮肤病学 | 14篇 |
神经病学 | 85篇 |
特种医学 | 1篇 |
外科学 | 18篇 |
综合类 | 2篇 |
眼科学 | 3篇 |
药学 | 7篇 |
中国医学 | 1篇 |
肿瘤学 | 3篇 |
出版年
2023年 | 1篇 |
2022年 | 3篇 |
2021年 | 6篇 |
2020年 | 3篇 |
2019年 | 3篇 |
2018年 | 4篇 |
2017年 | 5篇 |
2016年 | 1篇 |
2015年 | 3篇 |
2014年 | 9篇 |
2013年 | 7篇 |
2012年 | 5篇 |
2011年 | 4篇 |
2010年 | 6篇 |
2009年 | 8篇 |
2008年 | 5篇 |
2007年 | 5篇 |
2006年 | 7篇 |
2005年 | 4篇 |
2004年 | 5篇 |
2003年 | 6篇 |
2002年 | 2篇 |
2001年 | 3篇 |
2000年 | 3篇 |
1999年 | 1篇 |
1998年 | 6篇 |
1997年 | 4篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 12篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1989年 | 4篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 4篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1979年 | 2篇 |
1976年 | 2篇 |
1973年 | 1篇 |
排序方式: 共有175条查询结果,搜索用时 15 毫秒
1.
《European journal of medical genetics》2021,64(12):104345
BackgroundEpidermolysis bullosa (EB) is a genodermatosis characterized by skin fragility and blisters with variable severity. Patients with Dystrophic EB (DEB) or Junctional EB (JEB) mainly present to clinic due to greater functional impairment. Pathogenic sequence variations in COL7A1 are implicated in DEB.ObjectiveWe have tried to decipher the molecular spectrum and genotype phenotype correlation of 21 Indian patients with EB.MethodsNext generation sequencing (NGS) was performed to determine the pathogenic variants. Sanger sequencing was also done for validation of the variants in eleven individuals.ResultsPathogenic variants were detected in 20 individuals (diagnostic yield of 95%). Majority of them (90%) had sequence variation in COL7A1 while two had pathogenic variants in ITGB4 and KRT14 respectively. Out of the 18 patients confirmed to have DEB, 3 had Dominant DEB (DDEB) whereas 15 patients had Recessive DEB (RDEB). Amongst 23 sequence variations identified, 12 were found to be novel (3 were missense, 5 were premature termination codon variants while 4 were splice-site changes).ConclusionGenotype phenotype correlation was noted with milder manifestations in those with dominant inheritance types. Exact molecular diagnosis can be ascertained by NGS in majority of cases. 相似文献
2.
In the past 5 years enormous progress have been made in our understanding of the molecular basis for a number of inherited skin diseases characterized by easy blistering of the skin and the mucous membranes after minor physical trauma. This increased fragility of the skin or its appendages is due to molecular defects in genes coding for different intra- and extracellular structural proteins which are responsible for mechanical strength at their sites of expression. These diseases encompass the group of epidermolysis bullosa and disorders of cornification such as bullous forms of ichthyosis, palmoplantar keratoderma, and pachyonychia congenita. On the basis of clinical, morphological, and ultrastructural observations the epidermolysis bullosa group has been divided into three major categories. In epidermolysis bullosa simplex blister formation appears within the basal cell layer of the epidermis, and many mutations have been found in the genes of keratin 5 and 14 which are both expressed in basal keratinocytes. Epidermolytic hyperkeratosis leads to an epidermal separation in the suprabasal cell layers. In these patients numerous point mutations have now been described in the suprabasally expressed genes of keratin 1 and 10. In ichthyosis bullosa of Siemens blisters occur in the more upper suprabasal epidermis coincidental with the expression of keratin 2e, and mutations have been detected in the corresponding gene. In epidermolytic palmoplantar hyperkeratosis the suprabasal epidermal splitting is restricted to palms and soles of the patient. In keratin 9, which reveals such an exclusive expression pattern, molecular defects have indeed been recognized. Most recently in two different clinical subtypes of pachyonychia congenita, which is characterized by defective nails and focal palmoplantar hyperkeratosis, point mutations have been found in the genes coding for keratins 6, 16, and 17. In junctional epidermolysis bullosa the separation takes place within the dermal-epidermal basement membrane at the level of the lamina lucida, and mutations have been found in three genes coding for different laminin chains, in the 4 gene of 64 integrin, and in the gene of collagen XVII. In dystrophic epidermolysis bullosa the tissue separation occurs beneath the basement membrane within the papillary dermis at the level of the anchoring fibrils, and several mutations have been identified in the collagen VII gene. The rapid unraveling of molecular defects in these disabling or even lethal inherited skin diseases makes possible a more precise and earlier prenatal diagnosis, creates new options for suitable therapeutic regimens, and even offers the hope of curing these diseases by means of somatic cell gene therapy.Abbreviations
BM
Basement membrane
-
BPAg
Bullous pemphigoid antigen
-
DEB
Dystrophic epidermolysis bullosa
-
EB
Epidermolysis bullosa
-
EBS
Epidermolysis bullosa simplex
-
EHK
Epidermolytic hyperkeratosis
-
EPPK
Epidermolytic palmoplantar keratoderma
-
IBS
Ichthyosis bullosa of Siemens
-
JEB
Junctional epidermolysis bullosa
-
KIF
Keratin intermediate filaments
-
NC
Noncollagenous domain
-
NEPPK
Nonepidermolytic palmoplantar keratoderma
-
PC
Pachyonychia congenita 相似文献
3.
Cholinesterases colocalize with sites of neurofibrillary degeneration in aged and Alzheimer's brains
Acetylcholinesterase and butyrylcholinesterase have been associated with structures undergoing neurofibrillary degeneration, as well as with all types of senile plaques, in non-demented aged and Alzheimer's brains. At the electron microscope level, the reaction product of both enzymes, appeared to decorate paired helical filaments, straight filaments and A4 amyloid fibrils. Recent studies showed that cholinesterases were associated with amyloid at early stages, e.g., in diffuse plaques. In the present study, the interrelationship of cholinesterases to structures undergoing neurofibrillary degeneration was analyzed further. Tau immunoreactivity was compared to the staining pattern observed with the two esterases. Double protocols consecutively performed on the same sections, and counterstaining with thioflavin-S, confirmed the presence of cholinesterases in all structures with neurofibrillary degeneration. The conclusion that cholinesterases consistently colocalize with both neurofibrillary bundles and A4 amyloid fibrils at all stages of their accumulation, allows us to speculate on the possible role that these enzymes may play in either the formation or the consolidation of fibrillary aggregates.Supported by Fondo de Investigaciones Sanitarias de la Seguridad Social No. 93/0198, Spain 相似文献
4.
Accelerated Differentiation in Response to Retinoic Acid After Retrovirally Mediated Gene Transfer of GAP-43 into Mouse Neuroblastoma Cells 总被引:2,自引:0,他引:2
Although substantial evidence exists for the involvement of growth-associated protein-43 (GAP-43) in neuronal development and regeneration, the precise role of this protein in neurite outgrowth is currently debated. To investigate the role of GAP-43 in the initiation of neurite outgrowth, we transfected a full-length cDNA coding for GAP-43 into a mouse neuroblastoma cell line (Neuro-2a) which can be differentiated to a neuronal phenotype using retinoic acid (RA). We show that the consequent overexpression of GAP-43 results in a change in the basic morphology of these cells, but is not in itself sufficient to induce the extension of neurites. However, overexpression of GAP-43 results in a marked acceleration of neurite formation in response to RA. We propose that while GAP-43 does not trigger the initiation of neurite extension, its expression is rate-limiting for neurite outgrowth in response to differentiation agents such as RA. 相似文献
5.
James A. Fyfe Lilia M. Beauchamp Anthony O. Caggiano Raymond D. Price Takayuki Yamaji Nobuya Matsuoka Thomas A. Krenitsky 《Drug development research》2004,62(1):49-59
The ability of endogenous neurotrophins, including nerve growth factor (NGF), to promote the survival and development of neurons provides convincing evidence for their therapeutic potential, despite significant barriers to their successful clinical use. Many of these barriers might be surmountable, however, by strategies that enhance endogenous neurotrophin signaling. We evaluated a series of substituted pyrimidines for their ability to enhance the effects of NGF. KP544 [2‐amino‐5‐(4‐chlorophenylethynyl)‐4‐(4‐trans‐hydroxycyclohexylamino) pyrimidine] amplified NGF‐induced neurite outgrowth of PC12 cells approximately 2‐fold at 2 µM. KP544 also enhanced choline acetyltransferase activity, a marker of differentiation induced by either NGF or by cyclic AMP, by 3‐ to 8‐fold, with a 2‐fold amplification at 0.12–0.3 µM. This amplification occurred at all concentrations of NGF used including those that maximally stimulated the cells. KP544 did not increase the levels of phosphorylated mitogen‐activated protein kinases (MAPK) above that seen with NGF alone. These studies suggested that KP544 functions within the cell at a site that is downstream from or independent of MAPK signaling. NGF‐induced neurite outgrowth in a human cell line (SH‐SY5Y neuroblastoma cells) was also enhanced with KP544 treatment. Primary embryonic rat cortical cultures were used to extend the observations beyond the studies with the immortalized cell lines. In addition to effects on neurite outgrowth, KP544 protected these cells from glutamate‐induced death. Overall, the data suggest that KP544 can selectively interact in the differentiation pathway downstream of MAPK in a manner that amplifies nerve growth factor and cyclic AMP effects and is also neuroprotective. Drug Dev. Res. 62:49–59, 2004. © 2004 Wiley‐Liss, Inc. 相似文献
6.
7.
8.
P. R. Venu Gopal P. Kumar George K. George Naveen Hood Lidiya James Milthi Manoj Joseph Francis 《The Indian journal of surgery》2014,76(5):378-381
The rare situation of thyroid stone is discussed with literature review and case report. A case of isolated solitary stone of the thyroid is documented here. There are incidences of calcification in the thyroid gland commonly associated with carcinoma thyroid and multinodular goiter. But solitary stone of thyroid is reported rarely and one such case is reported from India. The possibility of malignancy is high, in case of calcification of thyroid swellings. Hence, isolated calcification should be surgically treated even if fine needle aspiration cytology is negative for malignancy. 相似文献
9.
【摘要】 目的:探讨对伴有肋骨侵入椎管的Ⅰ型神经纤维瘤病营养不良型脊柱侧后凸(neurofibromatosis kyphoscoliosis type 1,NFK-1)患者行单纯后路矫形手术的安全性和早期临床治疗效果。方法:2003年2月~2013年4月共收治8例伴肋骨侵入椎管的Ⅰ型神经纤维瘤病患者,男6例,女2例;年龄7~24岁,平均12.9岁。所有病例肋骨侵入椎管内节段均在侧凸顶点附近1个椎体节段,术前肋骨椎管占位比平均32.86%。其中7例接受单纯后路矫形融合术,1例接受生长棒矫形,均未对突入椎管内肋骨进行直接干预。回顾性分析患者术前、术后及随访时的X线片、CT、脊髓造影后CT(CTM)或MRI,对侧后凸Cobb角、躯干偏移等参数进行测量和分析;同时复习病历,记录围手术期的并发症。结果:手术时间平均为3.3h,术中出血量平均为460ml。固定节段平均为10.1个节段。手术前后胸段冠状面Cobb角分别为67.00°和34.38°,平均矫形率为48.7%。矢状面Cobb角分别为62.50°和31.25°,平均矫形率为49.9%。平均随访时间22.9个月,末次随访时主胸弯冠状面Cobb角及矢状面Cobb角分别为35.75°和33.38°。手术前、后及随访时冠状面躯干平衡分别为35.88mm、15.63mm和14.00mm;矢状位躯干平衡分别为35.13mm、18.13mm和15.50mm。手术前、后椎体旋转度分别为2.25°和1.88°,顶椎偏距分别为49.38mm和35.81mm。7例患者术后复查CT肋骨椎管占位比由术前33.36%减小为术后26.57%;2例肋骨位置未见明显变化,5例肋骨不同程度复位。2例患者术前有胸痛症状,术后胸痛症状均缓解;1例术前右下肢巴氏征(+)、踝阵挛(+),术后3个月随访病理征转阴性,无神经系统并发症。结论:对于无神经损害症状伴有肋骨侵入椎管内的Ⅰ型神经纤维瘤病脊柱侧后凸患者,对胸段脊柱直接矫形是安全、有效的。 相似文献
10.
Koji Kamagata Christina Andica Taku Hatano Takashi Ogawa Haruka Takeshige-Amano Kotaro Ogaki Toshiaki Akashi Akifumi Hagiwara Shohei Fujita Shigeki Aoki 《中国神经再生研究》2020,(9):1590-1600
The prevalence of neurodegenerative diseases is increasing as human longevity increases. The objective biomarkers that enable the staging and early diagnosis of neurodegenerative diseases are eagerly anticipated. It has recently become possible to determine pathological changes in the brain without autopsy with the advancement of diffusion magnetic resonance imaging techniques. Diffusion magnetic resonance imaging is a robust tool used to evaluate brain microstructural complexity and integrity, axonal order, density, and myelination via the micron-scale displacement of water molecules diffusing in tissues. Diffusion tensor imaging, a type of diffusion magnetic resonance imaging technique is widely utilized in clinical and research settings;however, it has several limitations. To overcome these limitations, cutting-edge diffusion magnetic resonance imaging techniques, such as diffusional kurtosis imaging, neurite orientation dispersion and density imaging, and free water imaging, have been recently proposed and applied to evaluate the pathology of neurodegenerative diseases. This review focused on the main applications, findings, and future directions of advanced diffusion magnetic resonance imaging techniques in patients with Alzheimer's and Parkinson's diseases, the first and second most common neurodegenerative diseases, respectively. 相似文献