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排序方式: 共有269条查询结果,搜索用时 15 毫秒
1.
J?rg Müller Klaus Seppi Nadia Stefanova Werner Poewe Irene Litvan Gregor K Wenning 《Movement disorders》2002,17(5):1041-1045
The frequency and pathophysiology of freezing of gait (FoG) in atypical parkinsonism is unknown. We analysed the frequency of FoG in postmortem-confirmed atypical parkinsonian disorders (APD) comprising corticobasal degeneration (CBD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Sixty-six patients with pathologically confirmed APD (CBD, n = 13; DLB, n = 14; MSA, n = 15; PSP, n = 24) formed the basis for a multicenter clinicopathological study. Clinical features at first and last clinical visit were abstracted from patient records on standardized forms following strict instructions. At the first visit (median 36 months after symptom onset), 24% of APD had FoG (CBD, 8%; DLB, 21%; PSP, 25%; MSA, 40%). Logistic regression analysis showed a significant association of FoG and urinary incontinence (P = 0.04) at first visit. At last visit, 47% of APD had FoG (CBD, 25%; PSP, 53%; DLB, 54%; MSA, 54%). Clinicopathological correlation based on routine postmortem examination failed to identify a consistent neuropathological substrate of FoG. This study demonstrates that (1) FoG is common in APD, and (2) urinary incontinence is significantly associated with FoG in these disorders. Whether FoG and urinary incontinence share similar neuropathological substrates remains to be determined by future studies. 相似文献
2.
Djarmati A Hedrich K Svetel M Schäfer N Juric V Vukosavic S Hering R Riess O Romac S Klein C Kostic V 《Human mutation》2004,23(5):525
Mutations in the Parkin (PARK2) and the DJ1 (PARK7) gene cause early-onset Parkinson disease (EOPD). We tested 75 Serbian EOPD patients for mutations in both genes by conventional mutational screening (SSCP/dHPLC/sequencing) to detect small sequence alterations and by gene dosage studies (quantitative PCR) to reveal deletions or multiplications of one or more exons. A compound heterozygous Parkin mutation (exon deletion and point mutation; [c.836_972del]+[c.1411C>T]; +1 is first nucleotide of GenBank AB009973.1) was identified in a patient who showed a relatively benign course after a disease onset at 41 years. Another case had a heterozygous exon deletion in DJ1 ([c.253_322del]+[?]) and presented with an age at onset of 45 years and a rapid disease course. In conclusion, Parkin mutations are surprisingly rare in our Serbian EOPD sample, suggesting that the mutation rate depends on the ethnic origin of the patients. Although DJ1 mutations appear to be rare, we confirm their role in EOPD and demonstrate the importance of gene dosage studies. 相似文献
3.
Ioulia?Kobliakova Olga?Zatsepina Vera?Stefanova Vladimir?Polyakov Igor?KireevEmail author 《Chromosome research》2005,13(2):169-181
In this study we used a novel technique to reveal both longitudinal and transverse differentiation within mammalian mitotic
chromosomes. Structural changes in chromosomes that we term ‘differential decondensation’ were produced in cells that were
first incubated in hypotonic medium (15% Hanks’ solution), then adapted to normotonic conditions and thereafter exposed to
a second short hypotonic shock. Such a double hypotonic treatment (DHT) is not critical for cell viability, but considerably
elongates the G2 phase of the cell cycle. Giemsa staining of differentially decondensed chromosomes corresponds to standard
G-banding, but does not need the standard post-fixation treatment. Using ‘dynamic’ BrdU banding, we show that such ‘differential’
staining is a result of differential resistance of the R- and G-bands to DHT. Thus, early-replicating foci, markers of R-bands,
are localized in the peripheral chromatin halo, whereas late-replicating foci, corresponding to G-bands, remain associated
with the axial regions of chromatids. Remarkably, despite these major changes in the structure of the chromosomal bands, the
replication foci still preserve their discrete structure. 相似文献
4.
Dina Chelouche Lev Amir Onn Vladislava O Melinkova Claudia Miller Valerie Stone Maribelis Ruiz Eric C McGary Honnavara N Ananthaswamy Janet E Price Menashe Bar-Eli 《Journal of clinical oncology》2004,22(11):2092-2100
PURPOSE: In recent years, the incidence of cutaneous melanoma has increased more than that of any other cancer. Dacarbazine is considered the gold standard for treatment, having a response rate of 15% to 20%, but most responses are not sustained. Previously, we have shown that short exposure of primary cutaneous melanoma cells to dacarbazine resulted in the upregulation of interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF). The purpose of the present study was to determine how long-term exposure of melanoma cells to dacarbazine would affect their tumorigenic and metastatic potential in vivo. MATERIALS AND METHODS: The primary cutaneous melanoma cell lines SB2 and MeWo were repeatedly exposed in vitro to increasing concentrations of dacarbazine, and dacarbazine-resistant cell lines SB2-D and MeWo-D were selected and examined for their ability to grow and metastasize in nude mice. RESULTS: The dacarbazine-resistant cell lines SB2-D and MeWo-D exhibited increased tumor growth and metastatic behavior in vivo. This increase could be explained by the activation of RAF, MEK, and ERK, which led to the upregulation of IL-8 and VEGF. More IL-8, VEGF, matrix metalloproteinase-2 (MMP-2), and microvessel density (CD-31) were found in tumors produced by SB2-D and MeWo-D in vivo than in those produced by their parental counterparts. No mutations were observed in BRAF. CONCLUSION: Our results have significant clinical implications. Treatment of melanoma patients with dacarbazine could select for a more aggressive melanoma phenotype. We propose that combination treatment with anti-VEGF/IL-8 or MEK inhibitors may potentiate the therapeutic effects of dacarbazine. 相似文献
5.
6.
Over recent years, studies have demonstrated links between risk of cardiovascular disease in adulthood and adverse events that occurred very early in life during fetal development. The concept that there are embryonic and fetal adaptive responses to a sub-optimal intrauterine environment often brought about by poor maternal diet that result in permanent adverse consequences to life-long health is consistent with the definition of “programming”. The purpose of this review is to provide an overview of the current knowledge of the effects of intrauterine growth restriction (IUGR) on long-term cardiac structure and function, with particular emphasis on the effects of maternal protein restriction. Much of our recent knowledge has been derived from animal models. We review the current literature of one of the most commonly used models of IUGR (maternal protein restriction in rats), in relation to birth weight and postnatal growth, blood pressure and cardiac structure and function. In doing so, we highlight the complexity of developmental programming, with regards to timing, degree of severity of the insult, genotype and the subsequent postnatal phenotype. 相似文献
7.
Alexey A. Shadrin PhD Sören Mucha PhD David Ellinghaus PhD Mary B. Makarious BSc Cornelis Blauwendraat PhD Ashwin A.K. Sreelatha MSc Antonio Heras-Garvin PhD Jinhui Ding PhD Monia Hammer PhD Alexandra Foubert-Samier MD Wassilios G. Meissner MD Olivier Rascol PhD Anne Pavy-Le Traon MD Oleksandr Frei PhD Kevin S. O'Connell PhD Shahram Bahrami PhD Stefan Schreiber MD Wolfgang Lieb MD Martina Müller-Nurasyid PhD Ulf Schminke MD Georg Homuth PhD Carsten O. Schmidt PhD Markus M. Nöthen MD Per Hoffmann PhD Christian Gieger PhD Gregor Wenning MD for the European Multiple System Atrophy Study Group J. Raphael Gibbs PhD Andre Franke PhD John Hardy PhD Nadia Stefanova PhD Thomas Gasser MD Andrew Singleton PhD Henry Houlden MD Sonja W. Scholz MD Ole A. Andreassen PhD Manu Sharma PhD 《Movement disorders》2021,36(2):449-459
8.
9.
Marina V. Svetel Gordana Djuric Ivana Novakovic Valerija Dobricic Elka Stefanova Nikola Kresojevic Aleksandra Tomic Milena Jankovic Igor Petrovic Tatjana Pekmezovic Vladimir S. Kostic 《Acta neurologica Belgica》2013,113(3):243-245
Brain-derived neurotrophic factor (BDNF) modulates neuroplasticity. A functional polymorphism [Val66Met (G196A)] in BDNF has been reported to modify cortical plasticity in humans. Physiologic investigations have revealed that dystonia might be a consequence of the pathologic plasticity of the sensorimotor cortex. We aimed to investigate the role of the Val66Met polymorphism in a cohort of Serbian patients with adult-onset primary focal and segmental dystonia (PTD). One hundred and forty-nine patients with primary adult-onset PTD, 194 patients with Parkinson’s disease (PD), and 366 healthy control subjects were recruited for the study. Patients with PTD and PD, as well as healthy controls had a similar distribution of genotypes and allele frequencies. There was no any significant difference in the allelic distribution at the Val66Met SNP of the BDNF gene among patients with adult-onset PTD, PD, and healthy volunteers from the same geographic areas. In addition, the presence of the Met allele did not influence the clinical characteristics of PTD patients. Patients with the Met variant did not differ by age at onset, number of affected regions, and efficacy of a sensory trick. Met66Met is not associated with an increased risk of dystonia. 相似文献
10.
Expanding the clinical spectrum of the ‘HDAC8‐phenotype’ – implications for molecular diagnostics,counseling and risk prediction 下载免费PDF全文
I. Parenti C. Gervasini J. Pozojevic K.S. Wendt E. Watrin J. Azzollini D. Braunholz K. Buiting A. Cereda H. Engels L. Garavelli R. Glazar B. Graffmann L. Larizza H.J. Lüdecke M. Mariani M. Masciadri J. Pié F.J. Ramos S. Russo A. Selicorni M. Stefanova T.M. Strom R. Werner J. Wierzba G. Zampino G. Gillessen‐Kaesbach D. Wieczorek F.J. Kaiser 《Clinical genetics》2016,89(5):564-573
Cornelia de Lange syndrome (CdLS) is a clinically heterogeneous disorder characterized by typical facial dysmorphism, cognitive impairment and multiple congenital anomalies. Approximately 75% of patients carry a variant in one of the five cohesin‐related genes NIPBL, SMC1A, SMC3, RAD21 and HDAC8. Herein we report on the clinical and molecular characterization of 11 patients carrying 10 distinct variants in HDAC8. Given the high number of variants identified so far, we advise sequencing of HDAC8 as an indispensable part of the routine molecular diagnostic for patients with CdLS or CdLS‐overlapping features. The phenotype of our patients is very broad, whereas males tend to be more severely affected than females, who instead often present with less canonical CdLS features. The extensive clinical variability observed in the heterozygous females might be at least partially associated with a completely skewed X‐inactivation, observed in seven out of eight female patients. Our cohort also includes two affected siblings whose unaffected mother was found to be mosaic for the causative mutation inherited to both affected children. This further supports the urgent need for an integration of highly sensitive sequencing technology to allow an appropriate molecular diagnostic, genetic counseling and risk prediction. 相似文献