全文获取类型
收费全文 | 35643篇 |
免费 | 2261篇 |
国内免费 | 1469篇 |
专业分类
39373篇 |
出版年
2024年 | 94篇 |
2023年 | 600篇 |
2022年 | 804篇 |
2021年 | 1015篇 |
2020年 | 1103篇 |
2019年 | 1477篇 |
2018年 | 1293篇 |
2017年 | 935篇 |
2016年 | 960篇 |
2015年 | 1025篇 |
2014年 | 1851篇 |
2013年 | 2318篇 |
2012年 | 1423篇 |
2011年 | 1841篇 |
2010年 | 2147篇 |
2009年 | 1600篇 |
2008年 | 1588篇 |
2007年 | 1779篇 |
2006年 | 1539篇 |
2005年 | 1576篇 |
2004年 | 1563篇 |
2003年 | 1235篇 |
2002年 | 945篇 |
2001年 | 762篇 |
2000年 | 592篇 |
1999年 | 661篇 |
1998年 | 565篇 |
1997年 | 518篇 |
1996年 | 524篇 |
1995年 | 548篇 |
1994年 | 514篇 |
1993年 | 478篇 |
1992年 | 441篇 |
1991年 | 386篇 |
1990年 | 310篇 |
1989年 | 291篇 |
1988年 | 280篇 |
1987年 | 220篇 |
1986年 | 226篇 |
1985年 | 198篇 |
1984年 | 214篇 |
1983年 | 109篇 |
1982年 | 175篇 |
1981年 | 147篇 |
1980年 | 132篇 |
1979年 | 92篇 |
1978年 | 71篇 |
1977年 | 66篇 |
1976年 | 58篇 |
1972年 | 23篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
951.
《DNA Repair》2019
The bulk of DNA damage caused by ionizing radiation (IR) is generally repaired within hours, yet a subset of DNA lesions may persist even for long periods of time. Such persisting IR-induced foci (pIRIF) co-associate with PML nuclear bodies (PML-NBs) and are among the characteristics of cellular senescence. Here we addressed some fundamental questions concerning the nature and determinants of this co-association, the role of PML-NBs at such sites, and the reason for the persistence of DNA damage in human primary cells. We show that the persistent DNA lesions are devoid of homologous recombination (HR) proteins BRCA1 and Rad51. Our super-resolution microscopy-based analysis showed that PML-NBs are juxtaposed to and partially overlap with the pIRIFs. Notably, depletion of 53BP1 resulted in decreased intersection between PML-NBs and pIRIFs implicating the RNF168-53BP1 pathway in their interaction. To test whether the formation and persistence of IRIFs is PML-dependent and to investigate the role of PML in the context of DNA repair and senescence, we genetically deleted PML in human hTERT-RPE-1 cells. Unexpectedly, upon high-dose IR treatment, cells displayed similar DNA damage signalling, repair dynamics and kinetics of cellular senescence regardless of the presence or absence of PML. In contrast, the PML knock-out cells showed increased sensitivity to low doses of IR and DNA-damaging agents mitomycin C, cisplatin and camptothecin that all cause DNA lesions requiring repair by HR. These results, along with enhanced sensitivity of the PML knock-out cells to DNA-PK and PARP inhibitors implicate PML as a factor contributing to HR-mediated DNA repair. 相似文献
952.
953.
Ziliang Chen Yuan Ha Huaxian Jia Xiaoxiao Yan Mao Chen Miao Liu Renbing Wu 《Liver Transplantation》2019,9(19)
Construction of well‐defined metal–organic framework precursor is vital to derive highly efficient transition metal–carbon‐based electrocatalyst for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in water splitting. Herein, a novel strategy involving an in situ transformation of ultrathin cobalt layered double hydroxide into 2D cobalt zeolitic imidazolate framework (ZIF‐67) nanosheets grafted with 3D ZIF‐67 polyhedra supported on the surface of carbon cloth (2D/3D ZIF‐67@CC) precursor is proposed. After a low‐temperature pyrolysis, this precursor can be further converted into hybrid composites composed of ultrafine cobalt nanoparticles embedded within 2D N‐doped carbon nanosheets and 3D N‐doped hollow carbon polyhedra (Co@N‐CS/N‐HCP@CC). Experimental and density functional theory calculations results indicate that such composites have the advantages of a large number of accessible active sites, accelerated charge/mass transfer ability, the synergistic effect of components as well as an optimal water adsorption energy change. As a result, the obtained Co@N‐CS/N‐HCP@CC catalyst requires overpotentials of only 66 and 248 mV to reach a current density of 10 mA cm?2 for HER and OER in 1.0 m KOH, respectively. Remarkably, it enables an alkali‐electrolyzer with a current density of 10 mA cm?2 at a low cell voltage of 1.545 V, superior to that of the IrO2@CC||Pt/C@CC couple (1.592 V). 相似文献
954.
Henk‐Jan van den Ham Nadine A. Binai Fatiha Zaaraoui‐Boutahar Albert J. R. Heck Arno C. Andeweg 《Proteomics》2019,19(7)
Helper T cell differentiation is a key process in the regulation of adaptive immune responses. Here, mouse Th1 and Th2 cells are profiled using high‐throughput proteomics to increase the understanding of the molecular biology of Th differentiation to support the design of prophylactic and therapeutic intervention strategies for (infectious) diseases. Protein profiling of Th1/Th2 differentiated cells results in the quantification of almost 6000 proteins of which 41 are differentially expressed at FDR < 0.1, and 19 at the FDR < 0.05 level, respectively. Differential protein expression analysis identifies a number of the expected canonical Th differentiation markers, and gene set analysis using the REACTOME database and a hypergeometric test (FDR < 0.05) confirms that helper T cell pathways are the top sets that are differentially expressed. Additionally, by network analysis, many differentially expressed proteins are associated with the Th1 and Th2 pathways. Data are available via PRIDE database with identifier PXD004532. 相似文献
955.
A novel type of lipid droplet/lipoprotein (LD/LP) particle from Thermoplasma acidophilum has been identified recently, and based on biochemical evidences, it was named Thermoplasma Quinone Droplet (TaQD). The major components of TaQDs are menaquinones, and to some extent polar lipids, and the 153 amino acid long Ta0547 vitellogenin‐N domain protein. In this paper, the aim is to identify TaQD proteome components with 1D‐SDS‐PAGE/LC–MS/MS and cross reference them with Edman degradation. TaQD samples isolated with three different purification methods—column chromatography, immunoprecipitation, and LD ultracentrifugation—are analyzed. Proteins Ta0093, Ta0182, Ta0337, Ta0437, Ta0438, Ta0547, and Ta1223a are identified as constituents of the TaQD proteome. The majority of these proteins is uncharacterized and has low molecular weight, and none of them is predicted to take part in lipid metabolism. Bioinformatics analyses does not predict any interaction between these proteins, however, there are indications of interactions with proteins taking part in lipid metabolism. Whether if TaQDs provide platform for lipid metabolism and the interactions between TaQD proteins and lipid metabolism proteins occur in the reality remain for further studies. 相似文献
956.
Ajith Anand Emily Wu Zhi Li Sue TeRonde Maren Arling Brian Lenderts Jasdeep S. Mutti William Gordon‐Kamm Todd J. Jones Nicholas Doane Chilcoat 《Plant biotechnology journal》2019,17(8):1636-1645
An efficient Agrobacterium‐mediated site‐specific integration (SSI) technology using the flipase/flipase recognition target (FLP/FRT) system in elite maize inbred lines is described. The system allows precise integration of a single copy of a donor DNA flanked by heterologous FRT sites into a predefined recombinant target line (RTL) containing the corresponding heterologous FRT sites. A promoter‐trap system consisting of a pre‐integrated promoter followed by an FRT site enables efficient selection of events. The efficiency of this system is dependent on several factors including Agrobacterium tumefaciens strain, expression of morphogenic genes Babyboom (Bbm) and Wuschel2 (Wus2) and choice of heterologous FRT pairs. Of the Agrobacterium strains tested, strain AGL1 resulted in higher transformation frequency than strain LBA4404 THY‐ (0.27% vs. 0.05%; per cent of infected embryos producing events). The addition of morphogenic genes increased transformation frequency (2.65% in AGL1; 0.65% in LBA4404 THY‐). Following further optimization, including the choice of FRT pairs, a method was developed that achieved 19%–22.5% transformation frequency. Importantly, >50% of T0 transformants contain the desired full‐length site‐specific insertion. The frequencies reported here establish a new benchmark for generating targeted quality events compatible with commercial product development. 相似文献
957.
Zhefeng Wang Yilin Chen Xuwei Chen Xin Zheng Ganlin Xu Ziqiang Yuan Hui Zhao Wensheng Chen Lilin Li Nianjue Zheng Xiaotao Shen Yanmei Li Xufeng Qi Dongqing Cai 《Aging cell》2019,18(2)
The mechanism of age‐related decline in the angiogenic potential of the myocardium is not yet fully understood. Our previous report revealed that the aging of cardiac microvascular endothelial cells (CMECs) led to changes in their expression of receptor Trk isoforms: among the three isoforms (TrkB‐FL, TrkB‐T1 and TrkB‐T2), only the truncated TrkB‐T1 isoform continued to be expressed in aged CMECs, which led to decreased migration of CMECs in aging hearts. Thus far, how BDNF induces signalling through the truncated TrkB‐T1 isoform in aged CMECs remains unclear. Here, we first demonstrated that aged CMECs utilize BDNF–TrkB‐T1 signalling to recruit Willin as a downstream effector to further activate the Hippo pathway, which then promotes migration. These findings suggest that the aging process shifts the phenotype of aged CMECs that express TrkB‐T1 receptors by transducing BDNF signals via the BDNF–TrkB‐T1–Willin–Hippo pathway and that this change might be an important mechanism and therapeutic target of the dysfunctional cardiac angiogenesis observed in aged hearts. 相似文献
958.
In this study, for the first time, calcium oxide (CaO)/polylactic acid nanoscaffolds were synthesized by co‐precipitation assistant reverse micelles method. The physical and chemical (physicochemical) properties of the structures as dental resin composites were also studied. Nanocomposite materials as primary and basic dental compounds can be conveniently applied as dental filling materials with a high esthetic quality. In this research nanoscaffolds act as a bed for nanoparticles and improve the mechanical and chemical (mechanochemical) properties, CaO nanoparticles were loading in polylactic acid nanoscaffold as a bioactivity polymer for usage in the dental resin composites. Mechanical properties of the dental resin composite containing CaO/polylactic acid nanoscaffold were calculated: the flexural strength (137.2 MPa), modulus (12.9GPa) and compressive strength (344.2 MPa). Potential of the basic nanoparticle and the products were characterized by X‐ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), dynamic light scattering (DLS), ultraviolet‐visible spectroscopy (UV‐visible) and atomic force microscopy (AFM) showed the size of the optimized nanostructures was about 85 to 120 nm. According to TGA results of polylactic acid nanofibers with thermal stability below 300°C these high thermal stability materials can be used as dental resin composites. 相似文献
959.
Syeda Huma Bokhari Muhammad Mahmood-Ul-Hassan Munir Ahmad 《International journal of phytoremediation》2019,21(8):799-806
AbstractHeavy metals phytoextraction potential of swollen duckweed (Lemna gibba Linn.) and lesser duckweed (Lemna aequinoctialis Welw.) was determined under greenhouse conditions by exposing to untreated industrial/municipal effluent for a period of 21?days. The nickel (Ni), lead (Pb), and cadmium (Cd) concentrations in water samples were measured weekly and in plant biomass at the termination of experiments. Significant differences (p?<?0.05) between initial and final physicochemical parameters and in heavy metal concentrations of plant and water samples were observed. Periodically measured metal concentrations in mediums revealed that removal percentage was dependent on initial Ni (2.15?mg L?1), Pb (1.51?mg L?1), and Cd (0.74?mg L?1) concentrations. The final metal removal percentages were in the sequence of Ni (97%) > Pb (94%) > Cd (90%) when treated with Lemna gibba L. as compared to control (9–12% reduction). High biomass production of Lemna gibba L. resulted in a large metal reduction in the growth medium and the total plant metal contents were in the sequence of Ni (427?µg) > Pb (293?µg) > Cd (105?µg). The lesser duckweed did not survive under experimental conditions. Based on these results, we concluded that Lemna gibba L. is a good candidate for phytoremediation of wastewater. 相似文献
960.
《Molecular & cellular proteomics : MCP》2019,18(12):2492-2505
Highlights
- •Fast and culture-free method for the identification of the 15 bacterial species causing UTIs.
- •Combination of DIA analysis and machine learning algorithms to define a peptide signature.
- •High accuracy, good linearity and reproducibility, sensitivity below standard threshold.
- •Transferability to other laboratories and other mass spectrometers.