全文获取类型
收费全文 | 58200篇 |
免费 | 4618篇 |
国内免费 | 4542篇 |
专业分类
67360篇 |
出版年
2024年 | 149篇 |
2023年 | 798篇 |
2022年 | 1865篇 |
2021年 | 3051篇 |
2020年 | 2092篇 |
2019年 | 2522篇 |
2018年 | 2359篇 |
2017年 | 1823篇 |
2016年 | 2560篇 |
2015年 | 3645篇 |
2014年 | 4414篇 |
2013年 | 4455篇 |
2012年 | 5328篇 |
2011年 | 4797篇 |
2010年 | 2898篇 |
2009年 | 2619篇 |
2008年 | 2954篇 |
2007年 | 2648篇 |
2006年 | 2275篇 |
2005年 | 1896篇 |
2004年 | 1523篇 |
2003年 | 1426篇 |
2002年 | 1078篇 |
2001年 | 911篇 |
2000年 | 890篇 |
1999年 | 817篇 |
1998年 | 502篇 |
1997年 | 458篇 |
1996年 | 480篇 |
1995年 | 424篇 |
1994年 | 415篇 |
1993年 | 325篇 |
1992年 | 448篇 |
1991年 | 325篇 |
1990年 | 285篇 |
1989年 | 260篇 |
1988年 | 212篇 |
1987年 | 194篇 |
1986年 | 176篇 |
1985年 | 154篇 |
1984年 | 115篇 |
1983年 | 122篇 |
1982年 | 81篇 |
1981年 | 45篇 |
1980年 | 51篇 |
1979年 | 63篇 |
1976年 | 46篇 |
1974年 | 54篇 |
1973年 | 45篇 |
1972年 | 53篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
991.
Yue Yang Christine Shiao Jake Frederick Hemingway Nikolas L. Jorstad Bryan Richard Shalloway Rubens Chang C. Dirk Keene 《PloS one》2013,8(6)
Alzheimer''s disease (AD) is an age-related condition characterized by accumulation of neurotoxic amyloid β peptides (Aβ) in brain and retina. Because bone marrow transplantation (BMT) results in decreased cerebral Aβ in experimental AD, we hypothesized that BMT would mitigate retinal neurotoxicity through decreased retinal Aβ. To test this, we performed BMT in APPswe/PS1ΔE9 double transgenic mice using green fluorescent protein expressing wild type (wt) mice as marrow donors. We first examined retinas from control, non-transplanted, aged AD mice and found a two-fold increase in microglia compared with wt mice, prominent inner retinal Aβ and paired helical filament-tau, and decreased retinal ganglion cell layer neurons. BMT resulted in near complete replacement of host retinal microglia with BMT-derived cells and normalized total AD retinal microglia to non-transplanted wt levels. Aβ and paired helical filament-tau were reduced (61.0% and 44.1% respectively) in BMT-recipient AD mice, which had 20.8% more retinal ganglion cell layer neurons than non-transplanted AD controls. Interestingly, aged wt BMT recipients also had significantly more neurons (25.4%) compared with non-transplanted aged wt controls. Quantitation of retinal ganglion cell layer neurons in young mice confirmed age-related retinal degeneration was mitigated by BMT. We found increased MHC class II expression in BMT-derived microglia and decreased oxidative damage in retinal ganglion cell layer neurons. Thus, BMT is neuroprotective in age-related as well as AD-related retinal degeneration, and may be a result of alterations in innate immune function and oxidative stress in BMT recipient mice. 相似文献
992.
Chuanjiang Huang Yinan Luo Jingwei Zhao Fuwei Yang Hongwei Zhao Wenhai Fan Pengfei Ge 《PloS one》2013,8(6)
Background and Purpose
Shikonin was reported to induce necroptosis in leukemia cells, but apoptosis in glioma cell lines. Thus, it is needed to clarify whether shikonin could cause necroptosis in glioma cells and investigate its underlying mechanisms.Methods
Shikonin and rat C6 glioma cell line and Human U87 glioma cell line were used in this study. The cellular viability was assayed by MTT. Flow cytometry with annexin V-FITC and PI double staining was used to analyze cellular death modes. Morphological alterations in C6 glioma cells treated with shikoinin were evaluated by electronic transmission microscopy and fluorescence microscopy with Hoechst 33342 and PI double staining. The level of reactive oxygen species was assessed by using redox-sensitive dye DCFH-DA. The expressional level of necroptosis associated protein RIP-1 was analyzed by western blotting.Results
Shikonin induced cell death in C6 and U87 glioma cells in a dose and time dependent manner. The cell death in C6 and U87 glioma cells could be inhibited by necroptosis inhibitor necrotatin-1, not by pan-caspase inhibitor z-VAD-fmk. Shikonin treated C6 glioma cells presented electron-lucent cytoplasm, loss of plasma membrane integrity and intact nuclear membrane in morphology. The increased ROS level caused by shikonin was attenuated by necrostatin-1 and blocking ROS by anti-oxidant NAC rescued shikonin-induced cell death in both C6 and U87 glioma cells. Moreover, the expressional level of RIP-1 was up-regulated by shikonin in a dose and time dependent manner as well, but NAC suppressed RIP-1 expression.Conclusions
We demonstrated that the cell death caused by shikonin in C6 and U87 glioma cells was mainly via necroptosis. Moreover, not only RIP-1 pathway, but also oxidative stress participated in the activation of shikonin induced necroptosis. 相似文献993.
994.
Su Chia-Ying Lin Chun-Han Shih Pei-Ying Hsieh Chieh Yao Yu-Feng Tu Charng-Gan Chen Hao-Tsung Chen Horng-Shyang Kiang Yean-Woei Yang C. C. 《Plasmonics (Norwell, Mass.)》2016,11(3):931-939
Plasmonics - Surface plasmon (SP) coupling behaviors of an InGaN/GaN quantum well (QW) with surface plasmon polariton (SPP) induced on a smooth Ag-film/GaN interface and localized surface plasmon... 相似文献
995.
996.
A log-periodic toothed nanoantenna based on graphene is proposed, and its multi-resonance properties with respect to the variations of the chemical potential are investigated. The field enhancement and radar cross-section of the antenna for different chemical potentials are calculated, and the effect of the chemical potential on the resonance frequency is analyzed. In addition, the dependence of the resonance frequency on the substrate is also discussed. It is shown that large modulation of resonance intensity in log-periodic toothed nanoantenna can be achieved via turning the chemical potential of graphene. The tunability of the resonant frequencies of the antenna can be used to broad tuning of spectral features. The property of tunable multi-resonant field enhancement has great prospect in the field of graphene-based broadband nanoantenna, which can be applied in non-linear spectroscopy, optical sensor, and near-field optical microscopy. 相似文献
997.
998.
This paper proposes a road network growing model with the consideration of population distribution and central business district (CBD) attraction. In the model, the relative neighborhood graph (RNG) is introduced as the connection mechanism to capture the characteristics of road network topology. The simulation experiment is set up to illustrate the effects of population distribution and CBD attraction on the characteristics of road network. Moreover, several topological attributes of road network is evaluated by using coverage, circuitness, treeness and total length in the experiment. Finally, the suggested model is verified in the simulation of China and Beijing Highway networks. 相似文献
999.
Shuyan Ma Li Qing Xiaobo Yang Guiqiang Liang Li’e Zhang Qin Li Feng Xiong Suwan Peng Yifei Ma Xiaowei Huang Yunfeng Zou 《PloS one》2016,11(1)
Manganese (Mn) is an essential trace element, while excessive expose may induce neurotoxicity. Recently, lncRNAs have been extensively studied and it has been confirmed that lncRNAs participate in neural functions and aberrantly expressed lncRNAs are involved in neurological diseases. However, the pathological effects of lncRNAs on Mn-induced neurotoxicity remain unclear. In this study, the expression profiles of lncRNAs and messenger RNAs (mRNAs) were identified in Mn-treated hippocampal neurons and control neurons via microarray. Bioinformatic methods and intersection analysis were also employed. Results indicated that 566, 1161, and 1474 lncRNAs meanwhile 1848, 3228, and 4022 mRNAs were aberrantly expressed in low, intermediate, and high Mn-exposed groups compared with the control group, respectively. Go analysis determined that differentially expressed mRNAs were targeted to biological processes, cellular components, and molecular functions. Pathway analysis indicated that these mRNAs were enriched in insulin secretion, cell cycle, and DNA replication. Intersection analysis denominated that 135 lncRNAs and 373 mRNAs were consistently up-regulated while 150 lncRNAs and 560 mRNAs were consistently down-regulated. Meanwhile, lncRNA was significantly up-regulated while lncRNAs uc.229- and BC079195 were significantly down-regulated in three comparison groups. The relative expression levels of 3 lncRNAs and 4 mRNAs were validated through qRT-PCR. To the best of our knowledge, this study is the first to identify the expression patterns of lncRNAs and mRNAs in hippocampal neurons of Sprague–Dawley rats. The results may provide evidence on underlying mechanisms of Mn-induced neurotoxicity, and aberrantly expressed lncRNAs/mRNAs may be useful in further investigations to detect early symptoms of Mn-induced neuropsychiatric disorders in the central nervous system. BC089928相似文献
1000.
Ingrid C. Rulifson Ping Cao Li Miao David Kopecky Linda Huang Ryan D. White Kim Samayoa Jonitha Gardner Xiaosu Wu Kui Chen Trace Tsuruda Oliver Homann Helene Baribault Harvey Yamane Tim Carlson Jed Wiltzius Yang Li 《PloS one》2016,11(2)
Pancreatic amyloid formation by islet amyloid polypeptide (IAPP) is a hallmark pathological feature of type 2 diabetes. IAPP is stored in the secretory granules of pancreatic beta-cells and co-secreted with insulin to maintain glucose homeostasis. IAPP is innocuous under homeostatic conditions but imbalances in production or processing of IAPP may result in homodimer formation leading to the rapid production of cytotoxic oligomers and amyloid fibrils. The consequence is beta-cell dysfunction and the accumulation of proteinaceous plaques in and around pancreatic islets. Beta-site APP-cleaving enzyme 2, BACE2, is an aspartyl protease commonly associated with BACE1, a related homolog responsible for amyloid processing in the brain and strongly implicated in Alzheimer’s disease. Herein, we identify two distinct sites of the mature human IAPP sequence that are susceptible to BACE2-mediated proteolytic activity. The result of proteolysis is modulation of human IAPP fibrillation and human IAPP protein degradation. These results suggest a potential therapeutic role for BACE2 in type 2 diabetes-associated hyperamylinaemia. 相似文献