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101.
Jana Capkova Alena Kubatova Lukas Ded Olina Tepla Jana Peknicova 《Asian journal of andrology》2016,18(1):108-113
Recent studies have shown that infertility affects estimated 15% of all couples. Male infertility is the primary or contributory cause in 60% of these cases. Consequently, the application of assisted reproduction is increasing. These methods could benefit from an extended evaluation of sperm quality. For this reason, we analyzed sperm proteins from 30 men with normal spermiograms and 30 men with asthenozoospermia. Ejaculates of both groups were tested by flow cytometry (FCM) and fluorescence with a set of well-characterized anti-human sperm Hs-monoclonal antibodies (MoAbs), which were generated in our laboratory. No statistically significant differences were found between normospermics and asthenospermics in the expression of the sperm surface protein clusterin, evaluated with Hs-3 MoAb, and semenogelin, evaluated with Hs-9 MoAb. However, FCM revealed quantitative differences in the acrosomal proteins between normozoospermic and asthenozoospermic men, namely, in glyceraldehyde-3-phosphate dehydrogenase, evaluated with Hs-8 MoAb, valosin-containing protein, evaluated with Hs-14 MoAb, and ATP synthase (cAMP-dependent protein kinase II, PRKAR2A), evaluated with MoAb Hs-36. Asthenozoospermic men displayed a highly reduced expression of intra-acrosomal proteins, with a likely decrease in sperm quality, and thus a negative impact on successful reproduction. Asthenozoospermia seems to be a complex disorder involving intra-acrosomal proteins. 相似文献
102.
Alena Shyla Gabriele Hölzlwimmer Julia Calzada‐Wack Karin Bink Oleg Tischenko Marie‐Noëlle Guilly Sylvie Chevillard Elenore Samson Jochen Graw Michael J. Atkinson Natalia S. Pellegata 《International journal of cancer. Journal international du cancer》2010,126(10):2362-2372
Pheochromocytomas are neoplasias of neural crest origin that arise from the chromaffin cells of the adrenal medulla. Pheochromocytomas arise with complete penetrance in rats homozygous for a germ‐line frameshift mutation of Cdkn1b, encoding the cell cycle inhibitor p27KIP1 (MENX syndrome). We performed a genome‐wide scan for allelic imbalance comparing 20 rat pheochromocytoma DNAs with normal rat DNA to better understand the pathobiology of the tumors and to correlate the findings with human pheochromocytoma. We identified allelic imbalance (AI) at candidate regions on rat chromosomes 8 and 19. Interestingly, the regions often lost in rat tumors are syntenic to regions involved in human pheochromocytomas. Fluorescence in situ hybridization analysis further validated the AI data. Sdhd and Rassf1a were analyzed in detail as they map to regions of AI on chromosome 8 and their homologues are implicated in human pheochromocytoma: we found no genetic mutations nor decreased expression. We also analyzed additional candidate genes, that is, rat homologues of genes predisposing to human pheochromocytoma and known tumor‐suppressor genes, but we found no AI. In contrast, we observed frequent overexpression of Cdkn2a and Cdkn2c, encoding the cell cycle inhibitors p16INK4a and p18INK4c, respectively. The relative small number of allelic changes we found in rat pheochromocytoma might be related to their nonmalignant status and losses at chromosomes 8 and 19 are events that precede malignancy. Because of the high concordance of affected loci between rat and human tumors, studies of the MENX‐associated pheochromocytomas should facilitate the identification of novel candidate genes implicated in their human counterpart. 相似文献
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Atrasheuskaya AV Blatun EM Kulak MV Atrasheuskaya A Karpov IA Rubin S Ignatyev GM 《Vaccine》2007,25(24):4651-4658
The purpose of this study was to investigate mumps vaccine failures (VF) in a highly vaccinated population of Minsk, Belarus, and to investigate a possible role for virus strain-specific immunity. During our 3-year study period, 22 adults were admitted to the Infectious Diseases Hospital in Minsk with a diagnosis of mumps. A genotype H1 mumps virus (MuV) strain was identified in all patients. Of 15 patients from whom the paired sera were collected, 9 were confirmed to have been previously vaccinated. Serological examinations indicated primary VF in seven of these cases and secondary VF in two. Despite almost all vaccinated patients possessing MuV specific IgG, few possessed neutralizing antibody to the vaccine strain and titers were nominal. Importantly, none of the sera were able to neutralize a genotype H MuV strain. Our results demonstrate the importance of assaying for neutralizing antibody and support the assertion that antigenic differences between wild type and vaccine MuV strains may play a role in cases of breakthrough infection in vaccinees. 相似文献
105.
Kraml PJ Klein RL Huang Y Nareika A Lopes-Virella MF 《Metabolism: clinical and experimental》2005,54(4):453-459
Epidemiological studies have established that a high level of iron body stores is associated with increased risk of acute coronary heart disease. To explain this association, it has been proposed that iron catalyzes the production of highly reactive forms of free oxygen species, and thus, promotes low-density lipoprotein (LDL) oxidation, a lipoprotein that plays a critical role in atherogenesis. However, few studies have provided evidence to support this hypothesis. In the present study, we determined the effect of iron loading of THP-1 mononuclear phagocytes on LDL metabolism. We demonstrated that iron loading of THP-1 cells stimulated conjugated diene formation in LDL in the culture medium. In addition, iron loading of THP-1 cells significantly increased cholesteryl ester accumulation in cells exposed to native LDL, suggesting that during the incubation of the cells with native LDL, the LDL became oxidized and was taken up by the cells. We further demonstrated that the degradation of 125I-oxidized LDL was significantly increased in iron-loaded THP-1 cells. Lastly, we demonstrated that iron loading of THP-1 cells stimulated scavenger receptor expression in these cells. In conclusion, this study demonstrates that loading of mononuclear phagocytes with iron leads to oxidization of LDL, increased cellular cholesterol accumulation and scavenger receptor expression, and supports the hypothesis that increased macrophage iron levels promote atherogenesis. 相似文献
106.
Alena Svatkova René C.W. Mandl Thomas W. Scheewe Wiepke Cahn René S. Kahn Hilleke E. Hulshoff Pol 《Schizophrenia bulletin》2015,41(4):869-878
It has been shown that learning a new skill leads to structural changes in the brain. However, it is unclear whether it is the acquisition or continuous practicing of the skill that causes this effect and whether brain connectivity of patients with schizophrenia can benefit from such practice. We examined the effect of 6 months exercise on a stationary bicycle on the brain in patients with schizophrenia and healthy controls. Biking is an endemic skill in the Netherlands and thus offers an ideal situation to disentangle the effects of learning vs practice. The 33 participating patients with schizophrenia and 48 healthy individuals were assigned to either one of two conditions, ie, physical exercise or life-as-usual, balanced for diagnosis. Diffusion tensor imaging brain scans were made prior to and after intervention. We demonstrate that irrespective of diagnosis regular physical exercise of an overlearned skill, such as bicycling, significantly increases the integrity, especially of motor functioning related, white matter fiber tracts whereas life-as-usual leads to a decrease in fiber integrity. Our findings imply that exercise of an overlearned physical skill improves brain connectivity in patients and healthy individuals. This has important implications for understanding the effect of fitness programs on the brain in both healthy subjects and patients with schizophrenia. Moreover, the outcome may even apply to the nonphysical realm.Key words: physical exercise, schizophrenia, diffusion tensor imaging, connectivity, longitudinal, fractional anisotropy 相似文献
107.
Detecting AGG Interruptions in Male and Female FMR1 Premutation Carriers by Single‐Molecule Sequencing 下载免费PDF全文
Simon Ardui Valerie Race Alena Zablotskaya Matthew S. Hestand Hilde Van Esch Koenraad Devriendt Gert Matthijs Joris R. Vermeesch 《Human mutation》2017,38(3):324-331
The FMR1 gene contains an unstable CGG repeat in its 5′ untranslated region. Premutation alleles range between 55 and 200 repeat units and confer a risk for developing fragile X‐associated tremor/ataxia syndrome or fragile X‐associated primary ovarian insufficiency. Furthermore, the premutation allele often expands to a full mutation during female germline transmission giving rise to the fragile X syndrome. The risk for a premutation to expand depends mainly on the number of CGG units and the presence of AGG interruptions in the CGG repeat. Unfortunately, the detection of AGG interruptions is hampered by technical difficulties. Here, we demonstrate that single‐molecule sequencing enables the determination of not only the repeat size, but also the complete repeat sequence including AGG interruptions in male and female alleles with repeats ranging from 45 to 100 CGG units. We envision this method will facilitate research and diagnostic analysis of the FMR1 repeat expansion. 相似文献
108.
Intrathecal enzyme replacement therapy reverses cognitive decline in mucopolysaccharidosis type I 下载免费PDF全文
Igor Nestrasil Elsa Shapiro Alena Svatkova Patricia Dickson Agnes Chen Amy Wakumoto Alia Ahmed Edward Stehel Sarah McNeil Curtis Gravance Elizabeth Maher 《American journal of medical genetics. Part A》2017,173(3):780-783
Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal storage disease that seriously affects the brain. Severity of neurocognitive symptoms in attenuated MPS subtype (MPS IA) broadly varies partially, due to restricted permeability of blood‐brain barrier (BBB) which limits treatment effects of intravenously applied α‐L‐iduronidase (rhIDU) enzyme. Intrathecal (IT) rhIDU application as a possible solution to circumvent BBB improved brain outcomes in canine models; therefore, our study quantifies effects of IT rhIDU on brain structure and function in an MPS IA patient with previous progressive cognitive decline. Neuropsychological testing and MRIs were performed twice prior (baseline, at 1 year) and twice after initiating IT rhIDU (at 2nd and 3rd years). The difference between pre‐ and post‐treatment means was evaluated as a percentage of the change. Neurocognitive performance improved particularly in memory tests and resulted in improved school performance after IT rhIDU treatment. White matter (WM) integrity improved together with an increase of WM and corpus callosum volumes. Hippocampal and gray matter volume decreased which may either parallel reduction of glycosaminoglycan storage or reflect typical longitudinal brain changes in early adulthood. In conclusion, our outcomes suggest neurological benefits of IT rhIDU compared to the intravenous administration on brain structure and function in a single MPS IA patient. © 2017 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc. 相似文献
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