全文获取类型
收费全文 | 409篇 |
免费 | 32篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 11篇 |
妇产科学 | 11篇 |
基础医学 | 46篇 |
临床医学 | 32篇 |
内科学 | 53篇 |
皮肤病学 | 14篇 |
神经病学 | 101篇 |
特种医学 | 3篇 |
外科学 | 52篇 |
综合类 | 4篇 |
预防医学 | 35篇 |
眼科学 | 12篇 |
药学 | 36篇 |
中国医学 | 1篇 |
肿瘤学 | 27篇 |
出版年
2023年 | 9篇 |
2022年 | 17篇 |
2021年 | 31篇 |
2020年 | 9篇 |
2019年 | 32篇 |
2018年 | 30篇 |
2017年 | 16篇 |
2016年 | 12篇 |
2015年 | 11篇 |
2014年 | 15篇 |
2013年 | 24篇 |
2012年 | 36篇 |
2011年 | 27篇 |
2010年 | 17篇 |
2009年 | 13篇 |
2008年 | 24篇 |
2007年 | 15篇 |
2006年 | 16篇 |
2005年 | 19篇 |
2004年 | 13篇 |
2003年 | 11篇 |
2002年 | 14篇 |
2001年 | 3篇 |
2000年 | 2篇 |
1999年 | 4篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1981年 | 1篇 |
1935年 | 2篇 |
1934年 | 2篇 |
排序方式: 共有441条查询结果,搜索用时 15 毫秒
111.
Edoardo Ferlazzo †Constant K. Adjien ‡§Renzo Guerrini †Tiziana Calarese ¶Arielle Crespel Maurizio Elia ††Pasquale Striano ¶Philippe Gelisse Placido Bramanti Paolo di Bella †Pierre Genton 《Epilepsia》2009,50(6):1587-1595
Purpose: Lennox-Gastaut syndrome (LGS) is a severe epileptic condition characterized by multiple seizure types including tonic seizures, slow spike-and-wave discharges on electroencephalography (EEG), and cognitive impairment. LGS can occur in apparently healthy subjects or in patients with preexisting brain damage. The onset peaks between 3 and 5 years of age and the prognosis is usually poor. Herein we report 13 subjects with trisomy 21 who developed LGS.
Methods: We retrospectively reviewed the clinical and EEG data of consecutive patients with LGS and trisomy 21 referred to five epilepsy centers over the last 30 years.
Results: Data for 13 patients (8 male, 5 female) were collected. The mean age at onset was 9.1 years (range 5–16). The mean age at last follow-up was 23.5 years (range 11–43 years). Seizure onset was after age 8 years in eight (62%) patients and between age 5 and 8 in the other five. In none of the cases did a West syndrome precede the onset of LGS. Nine of 13 patients (69%) had unambiguous reflex seizures, mostly precipitated by sudden unexpected sensory stimulations, usually preceding or accompanying the onset of a full-blown LGS picture. Interictal and ictal EEG findings were typical for LGS. All patients were drug-resistant.
Discussion: Patients with trisomy 21 may present a peculiar LGS, characterized by late onset and high occurrence of reflex seizures. Mechanisms underlying this particular presentation of LGS may include dendritic rarefaction and decreased interneurons, as well as functional abnormalities leading to overall decreased brain inhibition in these patients. 相似文献
Methods: We retrospectively reviewed the clinical and EEG data of consecutive patients with LGS and trisomy 21 referred to five epilepsy centers over the last 30 years.
Results: Data for 13 patients (8 male, 5 female) were collected. The mean age at onset was 9.1 years (range 5–16). The mean age at last follow-up was 23.5 years (range 11–43 years). Seizure onset was after age 8 years in eight (62%) patients and between age 5 and 8 in the other five. In none of the cases did a West syndrome precede the onset of LGS. Nine of 13 patients (69%) had unambiguous reflex seizures, mostly precipitated by sudden unexpected sensory stimulations, usually preceding or accompanying the onset of a full-blown LGS picture. Interictal and ictal EEG findings were typical for LGS. All patients were drug-resistant.
Discussion: Patients with trisomy 21 may present a peculiar LGS, characterized by late onset and high occurrence of reflex seizures. Mechanisms underlying this particular presentation of LGS may include dendritic rarefaction and decreased interneurons, as well as functional abnormalities leading to overall decreased brain inhibition in these patients. 相似文献
112.
PURPOSE: Thresholds to pentylenetetrazol (PTZ) seizures were usually based only on clinical symptoms. Our purpose was to use electroclinical patterns to assess the efficacy of a ketogenic and/or calorie-restricted diet on PTZ-induced seizures. METHODS: Forty 50-day-old rats were divided in four weight-matched groups and fed controlled diets: normocalorie carbohydrate (NC), hypocalorie carbohydrate (HC), normocalorie ketogenic (NK), and hypocalorie ketogenic (HK). After 21 days, blood glucose and beta-hydroxybutyrate levels were determined and seizures were induced by continuous infusion of PTZ. The clinical and EEG thresholds to each seizure pattern were compared between the different groups. RESULTS: The electroclinical course of PTZ-induced seizures was similar in all groups. The HK group exhibited higher thresholds than the other ones for most clinical features: absence (p = 0.003), first overt myoclonia (p = 0.028), clonic seizure (p = 0.006), and for EEG features: first spike (p = 0.036), first spike-and-wave discharge (p = 0.014), subcontinuous spike-and-wave discharges (p = 0.005). NK, HC, and NC groups were not significantly different from each other. Blood glucose and beta-hydroxybutyrate levels were not correlated with electroclinical seizure thresholds. After the clonic seizure, despite stopping PTZ infusion, a tonic seizure occurred in some animals, without significant difference regarding the diet. CONCLUSION: This approach permitted a precise study of the electroclinical course of PTZ-induced seizures. In addition to the usually studied first overt myoclonia, we clearly demonstrated the efficiency of a calorie restricted KD in elevating thresholds to most electroclinical seizure patterns. We confirmed the lack of efficiency of the KD to reduce seizure severity once the seizure has started. 相似文献
113.
The asymmetry of the fusiform face area is a stable individual characteristic that underlies the left-visual-field superiority for faces 总被引:1,自引:0,他引:1
Recognition of faces is better when faces are presented in the left than right-visual-field. Furthermore, this perceptual asymmetry is a stable individual characteristic. Although it has been commonly assumed that the right hemispheric dominance for face processing underlies this left-visual-field superiority in face recognition, this neural-behavioral association has never been directly demonstrated. Here we applied functional MRI (fMRI) to measure the magnitude of the asymmetric response to faces for each subject. To determine whether the asymmetric neural response to faces is stable across sessions, subjects returned for a second fMRI session. In addition, subjects performed a behavioral experiment outside the scanner where they had to recognize centrally presented chimeric faces, which presented different identities in the right- and left-visual-field. This task yielded a measure of the magnitude of the left-visual-field bias for each subject. Our findings show that the magnitude of the asymmetry of the face-selective area in the fusiform gyrus (FFA) is highly consistent for each individual across scans. We then show that the behavioral left-visual-field asymmetry, measured outside the scanner, was strongly and specifically correlated with the asymmetry of the FFA across subjects, but not with other face-specific or nearby object-general regions. Our findings provide the first empirical evidence for the prevalent idea that perceptual asymmetries in face recognition are associated with the well-known hemispheric asymmetry for faces. We conclude that the FFA asymmetry is a highly stable individual characteristic that underlies the well-established left-visual-field superiority for face recognition. 相似文献
114.
Hanaya R Koning E Ferrandon A Schweitzer A Andrieux A Nehlig A 《Journal of neuroscience research》2008,86(4):813-820
In mice, deletion of the STOP protein leads to subtle anatomic changes and induces depleted synaptic vesicle pools, impaired synaptic plasticity, hyperdopaminergy, and major behavioral disorders alleviated by neuroleptics, hence leading to a schizophrenic-like phenotype. In this study, we applied the quantitative autoradiographic [(14)C]2-deoxyglucose technique to study to what extent the basal rate of cerebral glucose utilization in STOP-knockout (STOP-KO) mice occurs in regions where metabolic changes have been reported in schizophrenic patients. Studies were performed on wild-type, heterozygous, and homozygous STOP-KO mice (7-8 per group). Mice were implanted with femoral artery and vein catheters, and cerebral glucose utilization was quantified over 45 min. Compared with that in wild-type mice, glucose utilization in STOP-KO mice was significantly increased in the olfactory cortex, ventromedial and anterolateral hypothalamus, ventral tegmental area, and substantia nigra pars compacta. Nonsignificant increases, ranging between 9% and 19%, were recorded in the whole auditory system, CA1 pyramidal cell layer, and dorsal raphe. Glucose utilization was also significantly increased in heterozygous mice compared with that in wild-type mice in olfactory cortex. These data might reflect hyperdopaminergic activity, olfactory deficits, and sleep disturbances in STOP-KO mice that have also been reported in schizophrenic patients. 相似文献
115.
The prevalence of epilepsy and pharmacoresistant epilepsy in adults: a population-based study in a Western European country 总被引:2,自引:0,他引:2
Purpose: To determine the prevalence of epilepsy in a defined adult population and identify the frequency and principal features of pharmacoresistant epilepsy.
Methods: From a population over 15 years of age residing in a medium-sized French city, all patients with epilepsy on June 30, 1995 were identified from multiple sources. Pharmacoresistance was defined as failure to control epilepsy by at least two first-line antiepileptic drugs, with a seizure frequency of at least one per month for 18 months. Collected data were examined by experts in epileptology, and responding patients were reexamined using a standardized diagnostic questionnaire. ILAE definitions and classifications were used.
Results: The age-adjusted prevalence of active epilepsy was 5.4 per 1,000 (95% CI: 4.7–6.0) and was higher for males (7.8) than for females (5.2). For epilepsy in remission under treatment, this rate was 0.7 per 1,000 (95% CI: 0.5–0.95). Age-specific prevalence was highest in age groups 25–49 years and declined in the oldest age groups. Localization-related seizures represented 61.1% of cases and generalized seizures 30.9%. The proportion of noncontrolled epilepsy (seizure-frequency at least one per month for 18 months) was 15.6%, corresponding to a prevalence of 0.94 per 1,000. In this group, the mean age at onset was lower (p = 0.0007) and localization-related epilepsy more frequent (p = 0.01).
Conclusion: The findings support previous epidemiological estimates of the prevalence of epilepsy in developed countries. For approximately one patient in eight, epilepsy was not adequately controlled. 相似文献
Methods: From a population over 15 years of age residing in a medium-sized French city, all patients with epilepsy on June 30, 1995 were identified from multiple sources. Pharmacoresistance was defined as failure to control epilepsy by at least two first-line antiepileptic drugs, with a seizure frequency of at least one per month for 18 months. Collected data were examined by experts in epileptology, and responding patients were reexamined using a standardized diagnostic questionnaire. ILAE definitions and classifications were used.
Results: The age-adjusted prevalence of active epilepsy was 5.4 per 1,000 (95% CI: 4.7–6.0) and was higher for males (7.8) than for females (5.2). For epilepsy in remission under treatment, this rate was 0.7 per 1,000 (95% CI: 0.5–0.95). Age-specific prevalence was highest in age groups 25–49 years and declined in the oldest age groups. Localization-related seizures represented 61.1% of cases and generalized seizures 30.9%. The proportion of noncontrolled epilepsy (seizure-frequency at least one per month for 18 months) was 15.6%, corresponding to a prevalence of 0.94 per 1,000. In this group, the mean age at onset was lower (p = 0.0007) and localization-related epilepsy more frequent (p = 0.01).
Conclusion: The findings support previous epidemiological estimates of the prevalence of epilepsy in developed countries. For approximately one patient in eight, epilepsy was not adequately controlled. 相似文献
116.
Cdric Schmidt Arielle L. Planchette David Nguyen Gabriel Giardina Yoan Neuenschwander Mathieu Di Franco Alessio Mylonas Adrien C. Descloux Enrico Pomarico Aleksandra Radenovic Jrme Extermann 《Biomedical optics express》2021,12(6):3619
Optical projection tomography (OPT) is a powerful tool for three-dimensional imaging of mesoscopic biological samples with great use for biomedical phenotyping studies. We present a fluorescent OPT platform that enables direct visualization of biological specimens and processes at a centimeter scale with high spatial resolution, as well as fast data throughput and reconstruction. We demonstrate nearly isotropic sub-28 µm resolution over more than 60 mm3 after reconstruction of a single acquisition. Our setup is optimized for imaging the mouse gut at multiple wavelengths. Thanks to a new sample preparation protocol specifically developed for gut specimens, we can observe the spatial arrangement of the intestinal villi and the vasculature network of a 3-cm long healthy mouse gut. Besides the blood vessel network surrounding the gastrointestinal tract, we observe traces of vasculature at the villi ends close to the lumen. The combination of rapid acquisition and a large field of view with high spatial resolution in 3D mesoscopic imaging holds an invaluable potential for gastrointestinal pathology research. 相似文献
117.
Seema R. Patel Chantel M. Cadwell Arielle Medford James C. Zimring 《The Journal of clinical investigation》2009,119(9):2787-2794
Bone marrow transplantation (BMT) represents a cure for nonmalignant hematological disorders. However, compared with the stringent conditioning regimens used when performing BMT to treat hematological malignancies, the reduced intensity conditioning regimen used in the context of nonmalignant hematological disorders leads to substantially higher rates of BMT rejection, presumably due to an intact immune system. The relevant patient population typically receives transfusion support, often including platelets, and the frequency of BMT rejection correlates with the frequency of transfusion. Here, we demonstrate that immunity to transfused platelets contributes to subsequent BMT rejection in mice, even when the BMT donor and recipient are MHC matched. We used MHC-matched bone marrow because, although immunity to transfused platelets is best characterized in relation to HLA-specific antibodies, such antibodies are unlikely to play a role in clinical BMT rejection that is HLA matched. However, bone marrow is not matched in the clinic for minor histocompatibility antigens, such as those carried by platelets, and we report that transfusion of minor histocompatibility antigen–mismatched platelets induced subsequent BMT rejection. These findings indicate previously unappreciated sequelae of immunity to platelets in the context of transplantation and suggest that strategies to account for minor histocompatibility mismatching may help to reduce the chance of BMT rejection in human patients. 相似文献
118.
Rufinamide (RUF) is a novel antiepileptic drug considered as second‐line therapy in the treatment of Lennox‐Gastaut syndrome. Treatment‐emergent adverse events (AEs) have consisted mainly of drowsiness, irritability, vomiting, and loss of appetite. RUF is considered as a “weight‐neutral” drug. We found clinically significant weight loss in 7 of 15 consecutive adult patients (47%; 3 male, 4 female, aged 18–31 years) treated with RUF as add‐on therapy (800–2,400 mg/day: 23.5–57.1 mg/kg/day). The body mass index (BMI) decreased by 7.3–18.7%. Two patients were obese class I before RUF. Five patients (71%) were underweight before RUF (mild in one case, moderate in two cases, and severe in two cases). Four of these patients stopped RUF because of this adverse effect. RUF was recommenced in two patients using a lower and slower dosing strategy; one patient showed improvement in seizure control and no weight loss but RUF was re‐stopped in the second patient because of continued weight loss. Despite of weight loss, RUF was continued in two other patients because it reduced seizure activity. We primarily related weight loss to reduced food intake, that is, loss of appetite and nausea, although in two patients no obvious loss of appetite was reported. RUF can cause clinically significant weight loss in adult patients, even at low dose. This AE can affect patients who are already underweight. There is a possibility that lower starting doses and slower escalation might minimize weight loss, but further information is required to determine whether this is the case. 相似文献
119.
Mathis C Ungerer A 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1999,129(1):147-155
The effects of immediate post-training administration of drugs interacting with group I and/or group II glutamate metabotropic
receptors (mGluRs) were determined on the retention performance of a partially acquired lever-press learning task in mice.
The antagonist (RS)-α-methyl-4-carboxyphenylglycine (MCPG) dose-dependently (0.1–100 nmol/mouse, i.c.v.) impairs the retention performance evaluated
24 h post-training. The retention deficit induced by 100 nmol MCPG is related to the selective suppression of a time-dependent
spontaneous improvement of performance between the two sessions. This phenomenon appears progressively within 24 h post-training
in control mice and is thought to reflect post-training processing of memory traces. The coadministration of either (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), the group I mGluR agonist (R,S)3,5-dihydroxyphenylglycine (DHPG), or the group II mGluR agonist LY354740, completely blocked MCPG-induced deficits at a
dose of 0.1 nmol for each agonist. These results suggest that selective activation of either group I or group II mGluRs is
able to prevent the memory retention deficits induced by MCPG.
Received: 27 January 1999 / Accepted: 27 May 1999 相似文献
120.