全文获取类型
收费全文 | 151篇 |
免费 | 4篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 13篇 |
妇产科学 | 20篇 |
基础医学 | 13篇 |
口腔科学 | 1篇 |
临床医学 | 10篇 |
内科学 | 23篇 |
皮肤病学 | 3篇 |
神经病学 | 26篇 |
外科学 | 7篇 |
综合类 | 3篇 |
预防医学 | 11篇 |
眼科学 | 1篇 |
药学 | 19篇 |
肿瘤学 | 3篇 |
出版年
2023年 | 2篇 |
2022年 | 3篇 |
2021年 | 7篇 |
2020年 | 5篇 |
2019年 | 4篇 |
2018年 | 1篇 |
2017年 | 3篇 |
2016年 | 3篇 |
2015年 | 1篇 |
2014年 | 3篇 |
2013年 | 8篇 |
2012年 | 12篇 |
2011年 | 13篇 |
2010年 | 6篇 |
2009年 | 4篇 |
2008年 | 9篇 |
2007年 | 11篇 |
2006年 | 7篇 |
2005年 | 12篇 |
2004年 | 14篇 |
2003年 | 8篇 |
2002年 | 6篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1998年 | 2篇 |
1995年 | 1篇 |
1991年 | 1篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1968年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有155条查询结果,搜索用时 15 毫秒
1.
Parkin localizes to the Lewy bodies of Parkinson disease and dementia with Lewy bodies 总被引:31,自引:0,他引:31 下载免费PDF全文
Schlossmacher MG Frosch MP Gai WP Medina M Sharma N Forno L Ochiishi T Shimura H Sharon R Hattori N Langston JW Mizuno Y Hyman BT Selkoe DJ Kosik KS 《The American journal of pathology》2002,160(5):1655-1667
Mutations in alpha-synuclein (alpha S) and parkin cause heritable forms of Parkinson disease (PD). We hypothesized that neuronal parkin, a known E3 ubiquitin ligase, facilitates the formation of Lewy bodies (LBs), a pathological hallmark of PD. Here, we report that affinity-purified parkin antibodies labeled classical LBs in substantia nigra sections from four related human disorders: sporadic PD, inherited alphaS-linked PD, dementia with LBs (DLB), and LB-positive, parkin-linked PD. Anti-parkin antibodies also detected LBs in entorhinal and cingulate cortices from DLB brain and alphaS inclusions in sympathetic gangliocytes from sporadic PD. Double labeling with confocal microscopy of DLB midbrain sections revealed that approximately 90% of anti-alpha S-reactive LBs were also detected by a parkin antibody to amino acids 342 to 353. Accordingly, parkin proteins, including the 53-kd mature isoform, were present in affinity-isolated LBs from DLB cortex. Fluorescence resonance energy transfer and immunoelectron microscopy showed that alphaS and parkin co-localized within brainstem and cortical LBs. Biochemically, parkin appeared most enriched in cytosolic and postsynaptic fractions of adult rat brain, but also in purified, alpha S-rich presynaptic elements that additionally contained parkin's E2-binding partner, UbcH7. We conclude that parkin and UbcH7 are present with alphaS in subcellular compartments of normal brain and that parkin frequently co-localizes with alpha S aggregates in the characteristic LB inclusions of PD and DLB. These results suggest that functional parkin proteins may be required during LB formation. 相似文献
2.
Inhibition of hepatitis C virus nonstructural protein, helicase activity, and viral replication by a recombinant human antibody clone 下载免费PDF全文
Prabhu R Khalap N Burioni R Clementi M Garry RF Dash S 《The American journal of pathology》2004,165(4):1163-1173
Hepatitis C virus (HCV) nonstructural protein 3 (NS3), with its protease, helicase, and NTPase enzymatic activities, plays a crucial role in viral replication, and therefore represents an ideal target for the development of anti-viral agents. We have developed a recombinant human antibody (Fab) that reacts with the helicase domain of HCV NS3. The affinity-purified Fab antibody completely inhibited the helicase activity of HCV NS3 at equimolar concentration. To evaluate the effect of the Fab on HCV replication, the clone encoding the Fab gene was put into an expression vector, which converts Fab into a complete IgG1 antibody. Using a DNA-based transfection model, we demonstrated that intracellular expression of this antibody resulted in significant reduction of HCV-negative strand RNA synthesis. Intracellular expression of this antibody into either a stable cell line replicating subgenomic RNA, or a transient full-length HCV replication model, reduced both HCV RNA and viral protein expression. These results support the use of recombinant antibody fragments to inhibit NS3 enzyme as a novel, feasible, and effective approach for inhibiting HCV replication. 相似文献
3.
Elena R. Schiff Malena Daich Varela Anthony G. Robson Karen Pierpoint Rola Ba‐Abbad Savita Nutan Wadih M. Zein Ehsan Ullah Laryssa A. Huryn Sari Tuupanen Omar A. Mahroo Michel Michaelides Derek Burke Katie Harvey Gavin Arno Robert B. Hufnagel Andrew R. Webster 《American journal of medical genetics. Part C, Seminars in medical genetics》2020,184(3):631-643
Pathogenic variants in the gene HGSNAT (heparan‐α‐glucosaminide N‐acetyltransferase) have been reported to underlie two distinct recessive conditions, depending on the specific genotype, mucopolysaccharidosis type IIIC (MPSIIIC)—a severe childhood‐onset lysosomal storage disorder, and adult‐onset nonsyndromic retinitis pigmentosa (RP). Here we describe the largest cohort to‐date of HGSNAT‐associated nonsyndromic RP patients, and describe their retinal phenotype, leukocyte enzymatic activity, and likely pathogenic genotypes. We identified biallelic HGSNAT variants in 17 individuals (15 families) as the likely cause of their RP. None showed any other symptoms of MPSIIIC. All had a mild but significant reduction of HGSNAT enzyme activity in leukocytes. The retinal condition was generally of late‐onset, showing progressive degeneration of a concentric area of paramacular retina, with preservation but reduced electroretinogram responses. Symptoms, electrophysiology, and imaging suggest the rod photoreceptor to be the cell initially compromised. HGSNAT enzymatic testing was useful in resolving diagnostic dilemmas in compatible patients. We identified seven novel sequence variants [p.(Arg239Cys); p.(Ser296Leu); p.(Phe428Cys); p.(Gly248Ala); p.(Gly418Arg), c.1543‐2A>C; c.1708delA], three of which were considered to be retina‐disease‐specific alleles. The most prevalent retina‐disease‐specific allele p.(Ala615Thr) was observed heterozygously or homozygously in 8 and 5 individuals respectively (7 and 4 families). Two siblings in one family, while identical for the HGSNAT locus, but discordant for retinal disease, suggest the influence of trans‐acting genetic or environmental modifying factors. 相似文献
4.
Linda T. Li Nutan B. Hebballi Eric W. Reynolds Seyed A. Arshad Gabrielle E. Hatton Dalya M. Ferguson Mary T. Austin Kevin P. Lally Kuojen Tsao 《Journal of pediatric surgery》2021,56(7):1113-1116
PurposeRepetitive painful stimuli and early exposure to opioids places neonates at risk for neurocognitive delays. We aimed to understand opioid utilization for neonates with gastroschisis.MethodsWe performed a retrospective review of infants with gastroschisis at a tertiary children's hospital (2017–2019). Multivariate linear regression was performed to analyze variations in opioid use.ResultsAmong 30 patients with gastroschisis, 33% were managed by primary suture-less closure, 7% by primary sutured closure, 40% by spring silo, and 20% by handsewn silo. The proportion of pain medication used was: morphine (89%), acetaminophen (8%), and fentanyl (3%). Opioids were used for a median of 6.5 days (range 0–20) per patient. Median total opioid administered across all patients was 2.2 morphine milligram equivalents (MME)/kg (IQR 0.7–3.3). Following definitive closure, median opioid use was 0.2 MME/kg (IQR 0.1–0.8). With multivariate regression, 45% of the variation in MME use was associated with the type of surgery after adjusting for weight, gestational age, and gender, p = 0.02. After definitive fascial closure, there was no significant variations in opioid use.ConclusionThere is a significant variation in the utilization of opioid, primarily prior to fascial closure. Understanding pain needs and standardization may improve opioid stewardship in infants with gastroschisis. 197/200Level of EvidenceLevel III 相似文献
5.
Chowdhary Kanika Kaushik Nutan 《Proceedings of the National Academy of Sciences, India. Section B.》2019,89(4):1379-1387
Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Microbial biopesticides offer an eco-friendly alternative to synthetic chemical pesticides. Bioassay-guided... 相似文献
6.
The deficits in operant behavior and the alterations in dendritic arborizations of Cornu Ammonis 1 and Cornu Ammonis 3 (CA1 and CA3) hippocampal areas were investigated in subicular lesioned rats. The subjects were female Wistar rats aged 120 days, and were divided into four groups: one serving as age-matched untrained control, a second group received training and sham lesioning, a third group were only trained, and the fourth group were first trained and then subjected to subicular lesions. The rats were food-deprived 24 hours prior to operant behavior training sessions. Two training sessions for operant behavior with continuous reinforcement of 10 minutes duration per day were done during the shaping session, following which rats were allowed 10 minutes of operant food reward for 10 days. On the eleventh day, only the operant behavior and sham-operated rats were used for subicular lesion and sham surgery, respectively. After 72 hours of surgical recovery, operant behavioral testing was performed daily as before for a further period of 10 days. Later, all groups of rats were killed and the hippocampus was processed for rapid Golgi staining. Our results suggest that subicular lesions produce a significant reduction in operant learning. Further, the Golgi studies revealed a reduction in dendritic branching points and intersections of apical and basal CA1, CA3 neurons in lesioned rats. 相似文献
7.
Ghosh SK Tiwari SN Sathyanarayan TS Sampath TR Sharma VP Nanda N Joshi H Adak T Subbarao SK 《Transactions of the Royal Society of Tropical Medicine and Hygiene》2005,99(2):101-105
Malaria was a major problem in a sericulture area of Karnataka, south India, where Anopheles culicifacies s.l. and A. fluviatilis s.l. were considered to be the main vectors. Sibling species complexes of these two species were analysed in three ecologically different villages. Among A. culicifacies, only sibling species A and B were found. In Puram, a village with 22 wells, species A predominated; species B predominated in a village with four wells and a stream, and in a village with a stream and no wells. Poecilia reticulata fish were introduced into all wells and streams in the villages, and after one year no vectors were found in Puram, and all, or nearly all, A. culicifacies were species B in the other two villages. All A. fluviatilis belonged to the sibling species T. Blood meal analysis indicated that a few of the A. culicifacies collected had fed on humans while all the A. fluviatilis had fed on bovines. Before the introduction of fish, the annual parasite incidence for malaria was high in Puram, but much lower in the other two villages. From 1998 (over one year after release of fish) until 2003, no malaria cases were detected in the three villages. 相似文献
8.
OBJECTIVE: In a previous study the authors found that dendritic spine density was reduced on prefrontal pyramidal neurons in layer 3 of subjects with schizophrenia. From a neural circuitry perspective, understanding the pathophysiological significance of this finding requires knowledge of whether pyramidal neurons in other cortical layers are similarly affected. The authors' goal was to determine whether their finding in layer 3 was also present in other cortical layers in the same group of subjects with schizophrenia. METHOD: Spine density and other dendritic measures were made for pyramidal neurons in layers 5 and 6 of prefrontal area 46 in the brains of deceased subjects with schizophrenia, subjects with other psychiatric disorders, and normal comparison subjects. RESULTS: None of the dendritic measures for layer 5 or 6 pyramidal neurons differed across the subject groups, but the within-subject differences in spine density between deep layer 3 and layer 5 or 6 pyramidal neurons were significantly greater in the patients with schizophrenia than in the comparison subjects. CONCLUSIONS: These findings are consistent with the idea that prefrontal pyramidal neurons involved in corticocortical and/or thalamocortical connections are preferentially affected in schizophrenia. 相似文献
9.
10.