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排序方式: 共有1444条查询结果,搜索用时 15 毫秒
41.
Alessandro Rufini Maria Victoria Niklison-Chirou Satoshi Inoue Richard Tomasini Isaac S. Harris Arianna Marino Massimo Federici David Dinsdale Richard A. Knight Gerry Melino Tak Wah Mak 《Genes & development》2012,26(18):2009-2014
Aging is associated with impaired scavenging of reactive oxygen species (ROS). Here, we show that TAp73, a p53 family member, protects against aging by regulating mitochondrial activity and preventing ROS accumulation. TAp73-null mice show more pronounced aging with increased oxidative damage and senescence. TAp73 deletion reduces cellular ATP levels, oxygen consumption, and mitochondrial complex IV activity, with increased ROS production and oxidative stress sensitivity. We show that the mitochondrial complex IV subunit cytochrome C oxidase subunit 4 (Cox4i1) is a direct TAp73 target and that Cox4i1 knockdown phenocopies the cellular senescence of TAp73-null cells. Results indicate that TAp73 affects mitochondrial respiration and ROS homeostasis, thus regulating aging. 相似文献
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A chronic low-grade inflammation is one of the hallmarks of the aging process. This gradually augmenting inflammatory state has been termed inflammaging. Inflammaging is associated with increased myelopoiesis in the bone marrow. This myelopoiesis-biased process increases the generation not only of mature myeloid cells, e.g. monocytes, macrophages, and neutrophils, but also immature myeloid progenitors and myeloid-derived suppressor cells (MDSCs). It is known that the aging process is associated with a significant increase in the presence of MDSCs in the bone marrow, blood, spleen, and peripheral lymph nodes. Consequently, MDSCs will become recruited into inflamed tissues where they suppress acute inflammatory responses and trigger the resolution of inflammation. However, if the perpetrator cannot be eliminated, the long-term presence of MDSCs suppresses the host’s immune defence and increases the susceptibility to infections and tumorigenesis. Chronic immunosuppression also impairs the clearance of waste products and dead cells, impairs energy metabolism, and disturbs tissue proteostasis. This immunosuppressive state is reminiscent of the immunosenescence observed in inflammaging. It seems that proinflammatory changes in tissues with aging stimulate the myelopoietic production of MDSCs which subsequently induces immunosenescence and maintains the chronic inflammaging process. We will briefly describe the functions of MDSCs and then examine in detail how inflammaging enhances the generation MDSCs and how MDSCs are involved in the control of immunosenescence occurring in inflammaging. 相似文献
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Cellular senescence refers to a process that cellular proliferation and differentiation modulated by the multiple stimulating factors gradually decline.Aging cells present the irreversible stop of proliferation and differentiation and change in secretory function because the cell cycle of aging cells is steadily blocked at some point. It has have been shown that cellular senescence plays an important role in the occurrence and development of liver diseases. In this paper, we review the advances in relations between cellular senescence and liver diseases. 相似文献
45.
Yuiko Koyano Gojiro Nakagami Takeo Minematsu Hiromi Sanada 《International wound journal》2018,15(5):807-813
The aim of this study was to compare protein secretion on intact skin of extremities and verify the relationship between the marker proteins on abdominal skin and systemic factors using skin blotting. A cross‐sectional study was conducted among elderly patients aged 65 years and older (N = 73) at a long‐term medical facility in Japan. Skin blotting was performed on the right and left forearms, right and left lower legs, and abdomen. Pearson's correlations and Bland–Altman plots were utilised for comparing the protein secretion from the skin between the right or left forearms or lower legs. Multiple regression analysis was applied to determine the relationship between intensity levels of 3 proteins on the abdominal skin and the systemic factors. Bland–Altman plots demonstrated that there was no significant difference between right and left secretion levels on the forearms and lower legs among 3 proteins. Multiple regression analysis showed that age and antiplatelet use was positively associated with decreased collagen type IV and increased matrix metalloproteinase 2 levels, respectively. Our findings suggested that collecting samples from either the right or the left skin would be sufficient if skin properties between arms and legs are evaluated using skin blotting. 相似文献
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Alexandra Vétillard Barbara Jonchère Marie Moreau Bertrand Toutain Cécile Henry Simon Fontanel Anne-Charlotte Bernard Mario Campone Catherine Guette Olivier Coqueret 《Oncotarget》2015,6(41):43342-43362
Activated in response to chemotherapy, senescence is a tumor suppressive mechanism that induces a permanent loss of proliferation. However, in response to treatment, it is not really known how cells can escape senescence and how irreversible or incomplete this pathway is. We have recently described that cells that escape senescence are more transformed than non-treated parental cells, they resist anoikis and rely on Mcl-1. In this study, we further characterize this emergence in response to irinotecan, a first line treatment used in colorectal cancer. Our results indicate that Akt was activated as a feedback pathway during the early step of senescence. The inhibition of the kinase prevented cell emergence and improved treatment efficacy, both in vitro and in vivo. This improvement was correlated with senescence inhibition, p21waf1 downregulation and a concomitant activation of apoptosis due to Noxa upregulation and Mcl-1 inactivation. The inactivation of Noxa prevented apoptosis and increased the number of emergent cells. Using either RNA interference or p21waf1-deficient cells, we further confirmed that an intact p53-p21-senescence pathway favored cell emergence and that its downregulation improved treatment efficacy through apoptosis induction. Therefore, although senescence is an efficient suppressive mechanism, it also generates more aggressive cells as a consequence of apoptosis inhibition. We therefore propose that senescence-inducing therapies should be used sequentially with drugs favoring cell death such as Akt inhibitors. This should reduce cell emergence and tumor relapse through a combined induction of senescence and apoptosis. 相似文献
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Kenneth W. Wachter Steven N. Evans David Steinsaltz 《Proceedings of the National Academy of Sciences of the United States of America》2013,110(25):10141-10146
W. D. Hamilton’s celebrated formula for the age-specific force of natural selection furnishes predictions for senescent mortality due to mutation accumulation, at the price of reliance on a linear approximation. Applying to Hamilton’s setting the full nonlinear demographic model for mutation accumulation recently developed by Evans, Steinsaltz, and Wachter, we find surprising differences. Nonlinear interactions cause the collapse of Hamilton-style predictions in the most commonly studied case, refine predictions in other cases, and allow walls of death at ages before the end of reproduction. Haldane’s principle for genetic load has an exact but unfamiliar generalization. 相似文献