全文获取类型
收费全文 | 27125篇 |
免费 | 2240篇 |
国内免费 | 1386篇 |
专业分类
30751篇 |
出版年
2024年 | 57篇 |
2023年 | 258篇 |
2022年 | 639篇 |
2021年 | 967篇 |
2020年 | 722篇 |
2019年 | 883篇 |
2018年 | 991篇 |
2017年 | 753篇 |
2016年 | 1166篇 |
2015年 | 1715篇 |
2014年 | 1998篇 |
2013年 | 2104篇 |
2012年 | 2490篇 |
2011年 | 2395篇 |
2010年 | 1471篇 |
2009年 | 1365篇 |
2008年 | 1650篇 |
2007年 | 1475篇 |
2006年 | 1320篇 |
2005年 | 1133篇 |
2004年 | 1107篇 |
2003年 | 896篇 |
2002年 | 748篇 |
2001年 | 397篇 |
2000年 | 316篇 |
1999年 | 286篇 |
1998年 | 230篇 |
1997年 | 177篇 |
1996年 | 167篇 |
1995年 | 129篇 |
1994年 | 119篇 |
1993年 | 67篇 |
1992年 | 94篇 |
1991年 | 72篇 |
1990年 | 83篇 |
1989年 | 68篇 |
1988年 | 49篇 |
1987年 | 46篇 |
1986年 | 28篇 |
1985年 | 27篇 |
1984年 | 36篇 |
1983年 | 14篇 |
1982年 | 10篇 |
1981年 | 8篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1967年 | 3篇 |
1965年 | 2篇 |
1962年 | 2篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
951.
Hyun-Su Lee Eun-Ju Choi Kyung-Sik Lee Hye-Ran Kim Bo-Ra Na Min-Sung Kwon Gil-Saeng Jeong Hyun Gyu Choi Eun Young Choi Chang-Duk Jun 《PloS one》2016,11(3)
Atopic dermatitis (AD) is a complex disease that is caused by various factors, including environmental change, genetic defects, and immune imbalance. We previously showed that p-hydroxycinnamic acid (HCA) isolated from the roots of Curcuma longa inhibits T-cell activation without inducing cell death. Here, we demonstrated that oral administration of HCA in a mouse model of ear AD attenuates the following local and systemic AD manifestations: ear thickening, immune-cell infiltration, production of AD-promoting immunoregulatory cytokines in ear tissues, increased spleen and draining lymph node size and weight, increased pro-inflammatory cytokine production by draining lymph nodes, and elevated serum immunoglobulin production. HCA treatment of CD4+ T cells in vitro suppressed their proliferation and differentiation into Th1 or Th2 and their Th1 and Th2 cytokine production. HCA treatment of keratinocytes lowered their production of the pro-inflammatory cytokines that drive either Th1 or Th2 responses in AD. Thus, HCA may be of therapeutic potential for AD as it acts by suppressing keratinocyte activation and downregulating T-cell differentiation and cytokine production. 相似文献
952.
Correction: Targeting Homologous Recombination in Notch-Driven C. elegans Stem Cell and Human Tumors
953.
Wenhua Li Aiyu Yao Hui Zhi Kuldeep Kaur Yong-chuan Zhu Mingyue Jia Hui Zhao Qifu Wang Shan Jin Guoli Zhao Zhi-Qi Xiong Yong Q. Zhang 《PLoS genetics》2016,12(5)
Altered expression of the E3 ubiquitin ligase UBE3A, which is involved in protein degradation through the proteasome-mediated pathway, is associated with neurodevelopmental and behavioral defects observed in Angelman syndrome (AS) and autism. However, little is known about the neuronal function of UBE3A and the pathogenesis of UBE3A-associated disorders. To understand the in vivo function of UBE3A in the nervous system, we generated multiple mutations of ube3a, the Drosophila ortholog of UBE3A. We found a significantly increased number of total boutons and satellite boutons in conjunction with compromised endocytosis in the neuromuscular junctions (NMJs) of ube3a mutants compared to the wild type. Genetic and biochemical analysis showed upregulation of bone morphogenetic protein (BMP) signaling in the nervous system of ube3a mutants. An immunochemical study revealed a specific increase in the protein level of Thickveins (Tkv), a type I BMP receptor, but not other BMP receptors Wishful thinking (Wit) and Saxophone (Sax), in ube3a mutants. Ube3a was associated with and specifically ubiquitinated lysine 227 within the cytoplasmic tail of Tkv, and promoted its proteasomal degradation in Schneider 2 cells. Negative regulation of Tkv by Ube3a was conserved in mammalian cells. These results reveal a critical role for Ube3a in regulating NMJ synapse development by repressing BMP signaling. This study sheds new light onto the neuronal functions of UBE3A and provides novel perspectives for understanding the pathogenesis of UBE3A-associated disorders. 相似文献
954.
955.
956.
Poly (ADP-ribose) polymerase (PARP) is a key molecule in the DNA damage response (DDR), which is a major target of both chemotherapies and radiotherapies. PARP inhibitors therefore comprise a promising class of anticancer therapeutics. In this study, we evaluated the efficacy of the PARP inhibitor olaparib, and also sought to identify the mechanism and predictive marker associated with olaparib sensitivity in head and neck cancer (HNC) cells. A total of 15 HNC cell lines, including AMC HNC cells, were tested. AMC-HN3 and HN4 exhibited stronger responses to olaparib. Among cisplatin-resistant cell lines, only AMC HN9-cisR cells were significantly suppressed by olaparib. We found that basal poly (ADP-ribose) (PAR) levels, but not PARP-1 levels, correlated with olaparib sensitivity. AMC-HN3 and HN4 cells exhibited higher basal levels of NF-κB that decreased significantly after olaparib treatment. In contrast, apoptotic proteins were intrinsically expressed in AMC-HN9-cisR cells. As interference with p53 expression led to NF-κB reactivation, we concluded that elevated basal PAR and NF-κB levels are predictive of olaparib responsiveness in HNC cells; in addition, olaparib inhibits HNC cells via PAR–p53–NF-κB interactions. 相似文献
957.
958.
Qianhui Xu Chang Liu Le Yang Peng Jin Chengchun Tang Zhongfang Chen 《Journal of molecular modeling》2016,22(8):184
Differing from the weakly antiaromatic B80 buckyball, the medium-sized C 1–B28 and D 2h –B38, as well as their mono- to tetra-anions, are highly aromatic, as indicated by the negative nucleus-independent chemical shifts (NICSs) at their cage centers. The interior cavities and high aromaticity of the B28 and B38 cages render them very promising hosts to accommodate diverse metal atoms. Accordingly, we carried out systematic density functional theory (DFT) computations on the structures, stabilities and electronic properties of metalloborofullerenes MB n (M?=?Li, Na, K, Rb, Cs, Be, Mg, Ca, Sr, Ba, Sc, Y, La and Ti; n?=?28 and 38). Among them, besides the recently reported M@B38(M?=?Sc, Y and Ti) [Lu et al. (2015) Phys Chem Chem Phys 17:20897–20902], Ti@B28 and M@B38 (M?=?Ca and La) also favor endohedral structures with large binding energies, and are suggested promising targets for experimental applications. Note that Ti@B28 is the first endohedral derivative based on the new B28 fullerene, and La@B38 features the largest metal size inside a B38 cage thus far. These endohedral derivatives, as exemplified by Ca@B38, may exhibit σ and π double aromaticity over the whole cage surface, indicating their considerable stability. In contrast, the other metals prefer to reside at the exterior cage surface, due mainly to the mismatch of their sizes with the boron cages, though the size match is not the only factor to determine their doping form. Furthermore, the infrared absorption spectra and 11B nuclear magnetic resonance spectra of the three new M@B n complexes were computed to assist future experimental characterization. 相似文献
959.
Nocturnal stridor is a breathing disorder prevalent in patients with multiple system atrophy (MSA). An improved understanding of this breathing disorder is essential since nocturnal stridor carries a poor prognosis (an increased risk of sudden death). In this study, we aimed to classify types of stridor by sound analysis and to reveal their clinical significance. Patients who met the criteria for probable MSA and had undergone polysomnography (PSG) were recruited. Patients were then assessed clinically with sleep questionnaires, including the Pittsburgh Sleep Quality Index, and the Hoehn and Yahr scale. Nocturnal stridor and snoring were analyzed with the Multi-Dimensional Voice Program. Nocturnal stridor was recorded in 22 patients and snoring in 18 patients using the PSG. Waveforms of stridors were classified into rhythmic or semirhythmic after analysis of the oscillogram. Formants and harmonics were observed in both types of stridor, but not in snoring. Of the 22 patients diagnosed with stridor during the present study, fifteen have subsequently died, with the time to death after the PSG study being 1.9 ± 1.4 years (range 0.8 to 5.0 years). The rhythmic waveform group presented higher scores on the Hoehn and Yahr scale and the survival outcome of this group was lower compared to the semirhythmic waveform group (p = 0.030, p = 0.014). In the Kaplan Meier’s survival curve, the outcome of patients with rhythmic waveform was significantly less favorable than the outcome of patients with semirhythmic waveform (log-rank test, p < 0.001). Stridor in MSA can be classified into rhythmic and semirhythmic types and the rhythmic component signifies a poorer outcome. 相似文献
960.
Pu Lv Haiqiang Jin Yuanyuan Liu Wei Cui Qing Peng Ran Liu Wei Sun Chenghe Fan Yuming Teng Weiping Sun Yining Huang 《PloS one》2016,11(3)