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121.
Bardet–Biedl syndrome (BBS) is a rare pediatric ciliopathy characterized by marked clinical variability and extensive genetic heterogeneity. Typical diagnosis of BBS is secured at a median of 9 years of age, and sometimes well into adolescence. Here, we report a patient in whom prenatal detection of increased nuchal fold, enlarged echogenic kidneys, and polydactyly prompted us to screen the most commonly mutated genes in BBS and the phenotypically and genetically overlapping ciliopathy, Meckel–Gruber syndrome (MKS). We identified the common Met390Arg mutation in BBS1 in compound heterozygosity with a novel intronic variant of unknown significance (VUS). Testing of mRNA harvested from primary foreskin fibroblasts obtained shortly after birth revealed the VUS to induce a cryptic splice site, which in turn led to a premature termination and mRNA degradation. To our knowledge, this is the earliest diagnosis of BBS in the absence of other affected individuals in the family, and exemplifies how combining clinical assessment with genetic and timely assays of variant pathogenicity can inform clinical diagnosis and assist with patient management in the prenatal and neonatal setting. 相似文献
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While our Y2K worries about old computers “retiring” at midnight captured the television and news media attention, a more significant “old age” phenomenon snuck onto the scene with hardly a headline: the dawn of the age of the aged.1 The over burdened health care system will face a worldwide wave of retirees who will live longer, cost more to treat, and demand new goods and services to help them stay healthy, active, and independent. Research in persuasive technologies and the associated usage of a computing system, device, or application intentionally designed to change a person's attitude or behavior in a predetermined way is showing the potential to assist in improving healthy living, reduce the costs on the health care system, and allow the aged to maintain a more independent life. This article gives a deeper insight into the evolution of persuasive technologies and presents a framework that can guide a researcher or practitioner in comprehending more effectively the work being done in this novel research field. It also provides categories of domains within health care in which these technologies are used and surveys exemplars from published literature. The article's goal is to provide greater understanding by addressing the challenges that lie ahead for all key stakeholders that design and/or use persuasive technologies in health care. 相似文献
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Tait D; Riccio M; Sittler A; Scherzinger E; Santi S; Ognibene A; Maraldi NM; Lehrach H; Wanker EE 《Human molecular genetics》1998,7(6):991-997
It has been reported that the ataxin-3 protein containing a polyglutamine
sequence in the pathological range (61-84Q) is localized within the nucleus
of neuronal cells, whereas ataxin-3 with a normal repeat length (12-37Q) is
predominantly a cytoplasmic protein. In this study, the subcellular
localization of the full-length ataxin-3 protein with a glutamine sequence
in the normal range (Q3KQ22) was analysed in two mammalian cell lines.
Using two affinity-purified polyclonal antibodies raised against the N- or
C-terminal portion of ataxin-3, the protein was detected predominantly, but
not exclusively, in the nucleus of COS-7 as well as neuroblastoma cells by
immunofluorescence and confocal laser scanning microscopy (CLSM). The
distribution of the protein in these cellular compartments was confirmed by
biochemical subcellular fractionations. Furthermore, CLSM revealed that the
ataxin- 3 protein present in the nucleus of neuroblastoma cells is
associated with the inner nuclear matrix. Our results taken together with
the finding of a nuclear localization signal in ataxin-3 indicate that the
ataxin-3 protein per se translocates to the nucleus and that an expanded
glutamine repeat is not essential for this transport.
相似文献
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Cardiovascular diseases are the major cause of death in the United States. The American Heart Association reports that approximately 500,000 persons die each year from heart attacks. Cardiac rehabilitation programs are based on objectives that would, when adhered to, extend and improve an individual's quality of life after experiencing a cardiac event. The purpose of this qualitative study was to explore and describe strategies that individuals who experienced a cardiac event used to overcome barriers associated with an exercise program. The sample consisted of six subjects (four females and two males) who were enrolled in a cardiac exercise program for 1 year or longer, and who continued to actively participate in at least two cardiac exercise classes per year. This study revealed that individuals who consistently participated in a cardiac exercise program did not use strategies to overcome barriers; rather, in their quest to survive, they used strategies to ensure their participation in the program. 相似文献
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129.
OBJECTIVE: To examine the influence of superoxide on the severity of collagen-induced arthritis (CIA) in mice. METHODS: CIA was induced in DBA/1J mice lacking the extracellular superoxide dismutase (EC-SOD) gene (knockout [KO]) and in normal DBA/1J mice (wild-type [WT]). RESULTS: The clinical disease activity score was significantly higher in EC-SOD-KO mice than in WT mice between days 36 and 53, and the histologic scores for joint damage on day 53 increased 2-fold or more in the EC-SOD-KO mice. There were no significant differences between the 2 groups of mice in proliferation indices of spleen or lymph node cells in vitro after stimulation with type II collagen. Although both IgG1 and IgG2a anticollagen antibody levels increased in both groups of mice between days 21 and 53, there were no significant differences between the 2 groups. Lipopolysaccharide-stimulated spleen cells from EC-SOD-KO mice produced greater levels of tumor necrosis factor alpha (TNFalpha) over 48 hours in culture compared with cells from WT mice. Increased steady-state levels of messenger RNA (mRNA) for interferon-gamma (IFNgamma), TNFalpha, and interleukin-1beta (IL-1beta), and lower levels of IL-1 receptor antagonist (IL-1Ra) mRNA were present in the joints of the EC-SOD-KO mice compared with the WT mice. CONCLUSION: The absence of EC-SOD leads to more severe CIA, which may be accompanied by enhanced production of the proinflammatory cytokines IFNgamma, TNFalpha, and IL-1beta, and decreased production of the antiinflammatory cytokine IL-1Ra in the joints. 相似文献
130.
EE Ekanem KI Eyong EE Philip-Ephraim ME Eyong EB Adams AA Asindi 《African health sciences》2013,13(4):1170-1173