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排序方式: 共有139条查询结果,搜索用时 15 毫秒
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van Slegtenhorst M; Nellist M; Nagelkerken B; Cheadle J; Snell R; van den Ouweland A; Reuser A; Sampson J; Halley D; van der Sluijs P 《Human molecular genetics》1998,7(6):1053-1057
Tuberous sclerosis (TSC) is an autosomal dominant disorder caused by a
mutation in either the TSC1 or TSC2 tumour suppressor gene. The disease is
characterized by a broad phenotypic spectrum that can include seizures,
mental retardation, renal dysfunction and dermatological abnormalities.
TSC2 encodes tuberin, a putative GTPase activating protein for rap1 and
rab5. The TSC1 gene was recently identified and codes for hamartin, a novel
protein with no significant homology to tuberin or any other known
vertebrate protein. Here, we show that hamartin and tuberin associate
physically in vivo and that the interaction is mediated by predicted
coiled-coil domains. Our data suggest that hamartin and tuberin function in
the same complex rather than in separate pathways.
相似文献
3.
Prospect for enzyme therapy in glycogenosis II variants: a study on cultured muscle cells 总被引:4,自引:0,他引:4
A. T. van der Ploeg P. A. Bolhuis R. A. Wolterman J. W. Visser M. C. B. Loonen H. F. M. Busch A. J. J. Reuser 《Journal of neurology》1988,235(7):392-396
Summary Impairment of skeletal muscle function is the common feature of distinct clinical forms of glycogenosis type II. In the present study, muscle cultures from different patients were used to investigate the cause of clinical heterogeneity and the feasibility of enzyme replacement therapy. The activity of acid -glucosidase appears to be the primary factor in determining the extent of lysosomal glycogen storage in muscle, and thereby the clinical severity of the disease. Neutral -glucosidases do not seem influencial. Correction of the enzymatic defect was achieved in skeletal muscle cultures from patients by administration of a high-uptake form of acid -glucosidase, purified from human urine. The enzyme reaches the lysosomes, including the glycogen storage vacuoles, and the lysosomal glycogen content is reduced to control level. In normal muscle cells 20% of the total cellular glycogen pool is segregated in lysosomal compartments. This percentage is higher than in fibroblasts, which may partly explain why muscles are more prone to store glycogen. The relevance of this study for enzyme therapy is discussed. 相似文献
4.
Verhell Coleta; de Graaff Graaff Esther; Bakker Cathy E.; Willemsen Rob; Willems Patric J.; Meijer Nicolle; Galjaard Hans; Reuser Arnold J.J.; Oostra Ben A.; Hoogeveen Andre 《Human molecular genetics》1995,4(5):895-901
FMR1 protein expression was studied in different tissues. Inhuman, monkey and murine tissues, high molecular mass FMR1 proteins(6780 kDa) are found, as shown in lymphobiastoid celiiines. The identity of these proteins was confirmed by theirabsence in tissues from patients with the fragile X syndromeand a FMR1 knock-out mouse. An IIe367Asn substitution in theFMR1 protein did not aiter the transiation, processing and localizationof FMR1 proteins in lymphoblastoid cells from a patient carryingthis mutation. All the high molecular mass FMR1 proteins isolatedfrom normal lymphoblastoid cells and cells from the patientwith the IIe367Asn substitution were able to bind RNA. However,the FMR1 proteins of the patient had reduced affinity for RNAbinding at high salt concentrations. In some human, monkey andmurine tissues low molecular mass FMR1 proteins (3941kDa) were found, which had the same N terminus as the 6790kDa isoforms, but differ in their C terminus and are thereforemost likely the result of carboxy-terminal proteolytic cleavage.These low molecular mass FMR1 proteins did not bind RNA, incontrast with the high molecular mass FMR1 proteins. The significanceof these low molecular mass proteins remains to be studied. 相似文献
5.
The European Journal of Health Economics - The COVID-19 pandemic has led to disruptions in healthcare utilization and spending. While some changes might persist (e.g. substitution of specialist... 相似文献
6.
Juna M. de Vries Nadine A.M.E. van der Beek Marian A. Kroos Lale Özkan Pieter A. van Doorn Susan M. Richards Crystal C.C. Sung Jan-Dietert C. Brugma Adrienne A.M. Zandbergen Ans T. van der Ploeg Arnold J.J. Reuser 《Molecular genetics and metabolism》2010,99(4):338-345
Clinical trials have demonstrated beneficial effects of enzyme replacement therapy (ERT) with alglucosidase alfa in infants, children and adults with Pompe disease. Recent studies have shown that high antibody titers can occur in patients receiving ERT and counteract the effect of treatment. This particularly occurs in those patients with classic-infantile Pompe disease that do not produce any endogenous acid α-glucosidase (CRIM-negative). It is still unclear to what extent antibody formation affects the outcome of ERT in adults with residual enzyme activity.We present the case of a patient with adult-onset Pompe disease. He was diagnosed at the age of 39 years by enzymatic testing (10.7% residual activity in fibroblasts) and DNA analysis (genotype: c.-32-13T>G/p.Trp516X). Infusion-associated reactions occurred during ERT and the patient's disease progressed. Concurrently, the antibody titer rose to a similarly high level as reported for some CRIM-negative patients with classic-infantile Pompe disease.Using newly developed immunologic-assays we could calculate that approximately 40% of the administered alglucosidase alfa was captured by circulating antibodies. Further, we could demonstrate that uptake of alglucosidase alfa by cultured fibroblasts was inhibited by admixture of the patient's serum.This case demonstrates that also patients with an appreciable amount of properly folded and catalytically active endogenous acid α-glucosidase can develop antibodies against alglucosidase alfa that affect the response to ERT. 相似文献
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8.
Arnold J. J. Reuser Hannerieke Van den Hout Agnes G. A. Bijvoet Marian A. Kroos Martin P. Verbeet Ans T. Van der Ploeg 《European journal of pediatrics》2002,161(1):S106-S111
Pompe disease or glycogen storage disease type II (OMIM 232300) is a metabolic myopathy with a broad clinical spectrum. Generalised
muscle weakness combined with cardiomegaly presents within the first 3 months after birth, if the lysosomal α-glucosidase
(AGLU) deficiency is complete. Residual enzyme activity prevents cardiac involvement and delays onset of muscle weakness.
Enzyme therapy, by intravenous administration of acid AGLU, aims to supplement the missing enzyme activity. At the SHS symposium
on Glycogen Storage Diseases Type I and II, in Fulda, two interim accounts were given of studies on the efficacy of enzyme
therapy for Pompe disease; one with recombinant human acid AGLU produced in Chinese hamster ovary cells and the other with
the same enzyme produced in the milk of transgenic rabbits.Conclusion: this review focuses on the latter study, discusses the scientific, technological and commercial aspects of the enterprise,
and addresses the prospects and challenges of enzyme therapy for Pompe disease.
Published online: 13 August 2002 相似文献
9.
Van den Hout JM Kamphoven JH Winkel LP Arts WF De Klerk JB Loonen MC Vulto AG Cromme-Dijkhuis A Weisglas-Kuperus N Hop W Van Hirtum H Van Diggelen OP Boer M Kroos MA Van Doorn PA Van der Voort E Sibbles B Van Corven EJ Brakenhoff JP Van Hove J Smeitink JA de Jong G Reuser AJ Van der Ploeg AT 《Pediatrics》2004,113(5):e448-e457
10.