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91.
Reza Taherkhani Fatemeh Farshadpour Mohammad Reza Ravanbod 《Journal of neurovirology》2018,24(3):372-375
We report a case of vaccine-associated paralytic poliomyelitis (VAPP) in an immunocompromised patient with acute lymphocytic leukemia who was initially diagnosed with aseptic meningitis. Isolation of Sabin-like type 1 poliovirus from the patient’s cerebrospinal fluid made this a case of vaccine-related poliovirus (VRPV) infection. The patient developed paralysis and respiratory distress and deceased a few months after onset of paralysis with respiratory failure. This tragic case report highlights the emergence of VAPP and indicates the importance of timely diagnosis of VRPV infections to improve clinical management of VRPV-infected patients and to prevent the devastating consequences of silent introduction of VRPVs in treatment wards and eventually in the society. 相似文献
92.
Rebecca G. Smith Eilis Hannon Philip L. De Jager Lori Chibnik Simon J. Lott Daniel Condliffe Adam R. Smith Vahram Haroutunian Claire Troakes Safa Al-Sarraj David A. Bennett John Powell Simon Lovestone Leonard Schalkwyk Jonathan Mill Katie Lunnon 《Alzheimer's & dementia》2018,14(12):1580-1588
Introduction
Alzheimer's disease is a neurodegenerative disorder that is hypothesized to involve epigenetic dysregulation of gene expression in the brain.Methods
We performed an epigenome-wide association study to identify differential DNA methylation associated with neuropathology in prefrontal cortex and superior temporal gyrus samples from 147 individuals, replicating our findings in two independent data sets (N = 117 and 740).Results
We identify elevated DNA methylation associated with neuropathology across a 48-kb region spanning 208 CpG sites within the HOXA gene cluster. A meta-analysis of the top-ranked probe within the HOXA3 gene (cg22962123) highlighted significant hypermethylation across all three cohorts (P = 3.11 × 10?18).Discussion
We present robust evidence for elevated DNA methylation associated with Alzheimer's disease neuropathology spanning the HOXA gene cluster on chromosome 7. These data add to the growing evidence highlighting a role for epigenetic variation in Alzheimer's disease, implicating the HOX gene family as a target for future investigation. 相似文献93.
94.
Shahab Mahmoudvand Somayeh Shokri Reza Taherkhani Fatemeh Farshadpour 《World journal of gastroenterology : WJG》2019,25(1):42-58
Hepatocellular carcinoma(HCC) is the fifth most common cancer, and hepatitis C virus(HCV) infection plays a major role in HCC development. The molecular mechanisms by which HCV infection leads to HCC are varied. HCV core protein is an important risk factor in HCV-associated liver pathogenesis and can modulate several signaling pathways involved in cell cycle regulation, cell growth promotion, cell proliferation, apoptosis, oxidative stress and lipid metabolism. The dysregulation of signaling pathways such as transforming growth factor β(TGF-β), vascular endothelial growth factor(VEGF), Wnt/β-catenin(WNT), cyclooxygenase-2(COX-2) and peroxisome proliferator-activated receptor α(PPARα) by HCV core protein is implicated in the development of HCC. Therefore, it has been suggested that this protein be considered a favorable target for further studies in the development of HCC. In addition, considering the axial role of these signaling pathways in HCC, they are considered druggable targets for cancer therapy. Therefore, using strategies to limit the dysregulation effects of core protein on these signaling pathways seems necessary to prevent HCV-related HCC. 相似文献
95.
96.
Fahed AC Safa RM Haddad FF Bitar FF Andary RR Arabi MT Azar ST Nemer G 《Molecular genetics and metabolism》2011,102(2):181-188
Familial hypercholesterolemia (FH) is an inherited disease characterized by the deposition of LDL in tissues causing premature atherosclerosis. Many genes are implicated in FH resulting in a large variability in the phenotype. DNA sequencing of the LDLR gene was done for forty patients clinically diagnosed with homozygous FH and forty family members variably affected. Patients underwent noninvasive heart and vascular studies. Statistical and pedigree analyses were used to correlate the different genotypes with the phenotypes. The prevalence of homozygosity at the Lebanese allele (2043C>A) is 45%. However, 27.5% of the patients have no mutations at all in the LDLR gene, and 27.5% are either heterozygous for the 2043C>A mutation, heterozygous for a mutation in another exon of the LDLR gene, or combined heterozygous for two different mutations. We confirm previous reports on the higher prevalence of FH in Lebanon. Our results do, however contradict previous reports on an assumed higher prevalence among the Christian Lebanese. Mutations in the LDLR especially combined heterozygosity can cause a severe phenotype similar to the homozygous mutation in the Lebanese allele. This information is particularly important in targeting the more prevalent heterozygotes in the general population with early diagnosis and intervention. 相似文献
97.
Al-Sarraj S King A Troakes C Smith B Maekawa S Bodi I Rogelj B Al-Chalabi A Hortobágyi T Shaw CE 《Acta neuropathologica》2011,122(6):691-702
Neuronal cytoplasmic inclusions (NCIs) containing phosphorylated TDP-43 (p-TDP-43) are the pathological hallmarks of motor
neuron disease/amyotrophic lateral sclerosis (MND/ALS) and FTLD-TDP. The vast majority of NCIs in the brain and spinal cord
also label for ubiquitin and p62, however, we have previously reported a subset of TDP-43 proteinopathy patients who have
unusual and abundant p62 positive, TDP-43 negative inclusions in the cerebellum and hippocampus. Here we sought to determine
whether these cases carry the hexanucleotide repeat expansion in C9orf72. Repeat primer PCR was performed in 36 MND/ALS, FTLD-MND/ALS and FTLD-TDP cases and four controls. Fourteen individuals with
the repeat expansion were detected. In all the 14 expansion mutation cases there were abundant globular and star-shaped p62
positive NCIs in the pyramidal cell layer of the hippocampus, the vast majority of which were p-TDP-43 negative. p62 positive
NCIs were also abundant in the cerebellar granular and molecular layers in all cases and in Purkinje cells in 12/14 cases
but they were only positive for p-TDP-43 in the granular layer of one case. Abundant p62 positive, p-TDP-43 negative neuronal
intranuclear inclusions (NIIs) were seen in 12/14 cases in the pyramidal cell layer of the hippocampus and in 6/14 cases in
the cerebellar granular layer. This unusual combination of inclusions appears pathognomonic for C9orf72 repeat expansion positive MND/ALS and FTLD-TDP which we believe form a pathologically distinct subset of TDP-43 proteinopathies.
Our results suggest that proteins other than TDP-43 are binding p62 and aggregating in response to the mutation which may
play a mechanistic role in neurodegeneration. 相似文献
98.
Hortobágyi T Troakes C Nishimura AL Vance C van Swieten JC Seelaar H King A Al-Sarraj S Rogelj B Shaw CE 《Acta neuropathologica》2011,121(4):519-527
Optineurin (OPTN) is a multifunctional protein involved in vesicular trafficking, signal transduction and gene expression.
OPTN mutations were described in eight Japanese patients with familial and sporadic amyotrophic lateral sclerosis (FALS, SALS).
OPTN-positive inclusions co-localising with TDP-43 were described in SALS and in FALS with SOD-1 mutations, potentially linking two pathologically distinct pathways of motor neuron degeneration. We have explored the abundance
of OPTN inclusions using a range of antibodies in postmortem tissues from 138 cases and controls including sporadic and familial
ALS, frontotemporal lobar degeneration (FTLD) and a wide range of neurodegenerative proteinopathies. OPTN-positive inclusions
were uncommon and detected in only 11/32 (34%) of TDP-43-positive SALS spinal cord and 5/15 (33%) of FTLD-TDP. Western blot
of lysates from FTLD-TDP frontal cortex and TDP-43-positive SALS spinal cord revealed decreased levels of OPTN protein compared
to controls (p < 0.05), however, this correlated with decreased neuronal numbers in the brain. Large OPTN inclusions were not detected in
FALS with SOD-1 and FUS mutation, respectively, or in FTLD-FUS cases. OPTN-positive inclusions were identified in a few Alzheimer’s disease (AD)
cases but did not co-localise with tau and TDP-43. Occasional striatal neurons contained granular cytoplasmic OPTN immunopositivity
in Huntington’s disease (HD) but were absent in spinocerebellar ataxia type 3. No OPTN inclusions were detected in FTLD-tau
and α-synucleinopathy. We conclude that OPTN inclusions are relatively rare and largely restricted to a minority of TDP-43
positive ALS and FTLD-TDP cases. Our results do not support the proposition that OPTN inclusions play a central role in the
pathogenesis of ALS, FTLD or any other neurodegenerative disorder. 相似文献
99.
Safaï K Sodji M Kapella M Maubon A Servaud M Aubard Y 《Gynécologie, obstétrique & fertilité》2006,34(6):506-509
Chila?diti's syndrome is the association of a radiological and clinical semiology of the interposition of large colon or small intestine between the lower side of diaphragm and liver. We report the case of a 32-year-old woman, primigravida, who undergone a caesarean section at 39 weeks of amenorrhoea, for a clinical picture of persistent abdominal pain and a beginning hepatic cytolysis. The patient presented one day after the ceasarean section an occlusive syndrome of the small intestine. The etiology of the occlusion of the small intestine in post-partum was a Chila?diti's syndrome with inter hepatodiaphragmatic incarceration of the small intestine discovered at the computed tomography. An exploratory laparotomy confirmed and permitted to treat Chila?diti's syndrome complicated by an occlusion. 相似文献
100.
Claus S Fischer J Mégarbané H Mégarbané A Jobard F Debret R Peyrol S Saker S Devillers M Sommer P Damour O 《The Journal of investigative dermatology》2008,128(6):1442-1450
Cutis laxa (CL) is a rare genodermatosis, which is clinically and genetically heterogeneous. It is characterized by redundant, loose, sagging, and inelastic skin. In a consanguineous family from Lebanon with autosomal-recessive transmission, we identified a homozygous missense mutation (c.649T --> C; p.C217R) in the fibulin-5 gene (FBLN5), which was, to our knowledge, previously unreported. Small skin biopsies were performed, which permitted isolation of skin fibroblasts harboring this FBLN5 mutation; they exhibited a deficit in cell growth. A CL skin equivalent (CL-SE) model compared with control SE was successfully developed to define the behavior of CL fibroblasts in a three-dimensional model. There was increased cell death and a global extracellular matrix deficiency in the dermis of this CL-SE model, and a low level of the main elastic fiber expression. There was no basement membrane evident at the ultrastructural level, and type-VII collagen could not be detected at the histological level. This model reproduced some defects of the extracellular matrix and highlighted other defects, which occurred at the time of the basement membrane formation, which were not evident in skin from patients. This CL-SE model could be adapted to screen for therapeutically active molecules. 相似文献