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131.
Wei-Chien Huang Yi-Ling Hsieh Chao-Ming Hung Pei-Hsuan Chien Yu-Fong Chien Lei-Chin Chen Chih-Yen Tu Chia-Hung Chen Sheng-Chieh Hsu Yueh-Ming Lin Yun-Ju Chen 《PloS one》2013,8(12)
The multikinase inhibitor, sorafenib (Nexavar®, BAY43-9006), which inhibits both the Raf/MEK/ERK pathway and several receptor tyrosine kinases (RTKs), has shown significantly therapeutic benefits in advanced hepatocellular carcinoma (HCC). However, not all HCC patients respond to sorafenib well and new therapeutic strategies to optimize the efficacy of sorafenib are urgently required. Overexpression of breast cancer resistance protein (BCRP/ABCG2) mediates the drug-efflux of several tyrosine kinase inhibitors (TKIs) to attenuate their efficacy. This study aimed to investigate the role of BCRP/ABCG2 in the sensitivity of HCC to sorafenib. Our data showed that BCRP/ABCG2 mediated the efflux of sorafenib. Co-treatment with a BCRP/ABCG2 inhibitor greatly augmented the cytotoxicity of sorafenib in HCC cells. Similar results were also achieved by the competitive inhibitor of BCRP/ABCG2, gefitinib, in combination with sorafenib. These results suggest not only that BCRP/ABCG2 is a potential predictor for the sorafenib sensitivity in HCC, but also that blockage of BCRP/ABCG2 may be a potential strategy to increase the response of HCC cells to sorafenib. 相似文献
132.
Rui Zhang Zhigang Meng Tao Zhou Yong Deng Li Feng Yuan Wang Guoqing Sun Sandui Guo Maozhi Ren 《Plant signaling & behavior》2013,8(11)
FKBP12 encodes a prolyl isomerase and highly conserved in eukaryotic species. In yeasts and animals, FKBP12 can interact with rapamycin and FK506 to form rapamycin-FKBP12 and FK506-FKBP12 complex, respectively. In higher plants, FKBP12 protein lost its function to bind rapamycin and FK506. Early studies showed that yeast and human FKBP12 protein can restore the rapamycin sensitivity in Arabidopsis, but the used concentration is 100–1000 folds higher than that in yeast and animals. High concentration of drugs would increase the cost and cause the potential secondary effects on plant growth and development. Here we further discovered that BP12 plants generated in our previous study are hypersensitive to rapamycin at the concentration as low as that is effective in yeast and animals. It is surprising to observe that WT and BP12 plants are not sensitive to FK506 in normal growth condition. These findings advance the current understanding of rapamycin-TOR signaling in plants. 相似文献
133.
134.
Lisha Kuang Haiping Kou Zhongwen Xie Ying Zhou Xingang Feng Lei Wang Zhigang Wang 《DNA Repair》2013,12(1):27-37
DNA damage tolerance consisting of template switching and translesion synthesis is a major cellular mechanism in response to unrepaired DNA lesions during replication. The Rev1 pathway constitutes the major mechanism of translesion synthesis and base damage-induced mutagenesis in model cell systems. Rev1 is a dCMP transferase, but additionally plays non-catalytic functions in translesion synthesis. Using the yeast model system, we attempted to gain further insights into the non-catalytic functions of Rev1. Rev1 stably interacts with Rad5 (a central component of the template switching pathway) via the C-terminal region of Rev1 and the N-terminal region of Rad5. Supporting functional significance of this interaction, both the Rev1 pathway and Rad5 are required for translesion synthesis and mutagenesis of 1,N6-ethenoadenine. Furthermore, disrupting the Rev1–Rad5 interaction by mutating Rev1 did not affect its dCMP transferase, but led to inactivation of the Rev1 non-catalytic function in translesion synthesis of UV-induced DNA damage. Deletion analysis revealed that the C-terminal 21-amino acid sequence of Rev1 is uniquely required for its interaction with Rad5 and is essential for its non-catalytic function. Deletion analysis additionally implicated a C-terminal region of Rev1 in its negative regulation. These results show that a non-catalytic function of Rev1 in translesion synthesis and mutagenesis is mediated by its interaction with Rad5. 相似文献
135.
Zhigang Zhang Gia-Phong Vu Hao Gong Chuan Xia Yuan-Chuan Chen Fenyong Liu Jianguo Wu Sangwei Lu 《PloS one》2013,8(6)
External guide sequences (EGSs) are RNA molecules that consist of a sequence complementary to a target mRNA and recruit intracellular ribonuclease P (RNase P), a tRNA processing enzyme, for specific degradation of the target mRNA. We have previously used an in vitro selection procedure to generate EGS variants that efficiently induce human RNase P to cleave a target mRNA in vitro. In this study, we constructed EGSs from a variant to target the overlapping region of the S mRNA, pre-S/L mRNA, and pregenomic RNA (pgRNA) of hepatitis B virus (HBV), which are essential for viral replication and infection. The EGS variant was about 50-fold more efficient in inducing human RNase P to cleave the mRNA in vitro than the EGS derived from a natural tRNA. Following
Salmonella
-mediated gene delivery, the EGSs were expressed in cultured HBV-carrying cells. A reduction of about 97% and 75% in the level of HBV RNAs and proteins and an inhibition of about 6,000- and 130-fold in the levels of capsid-associated HBV DNA were observed in cells treated with
Salmonella
vectors carrying the expression cassette for the variant and the tRNA-derived EGS, respectively. Our study provides direct evidence that the EGS variant is more effective in blocking HBV gene expression and DNA replication than the tRNA-derived EGS. Furthermore, these results demonstrate the feasibility of developing
Salmonella
-mediated gene delivery of highly active EGS RNA variants as a novel approach for gene-targeting applications such as anti-HBV therapy. 相似文献
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138.
Aude Cincotta Thanh Thuy Nguyen Tu Julien L. Colaux Guy Terwagne Sylvie Derenne Pascal Godefroit Robert Carleer Christelle Anquetil Johan Yans 《Palaeontology》2020,63(5):841-863
A panel of geochemical techniques is used here to investigate the taphonomy of fossil feathers preserved in association with the skeleton of the Jurassic theropod Anchiornis huxleyi. Extant feathers were analysed in parallel to test whether the soft tissues morphologically preserved in the fossil also exhibit a high degree of chemical preservation. Scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) indicate that clays and iron oxide pseudomorphs occur in the surrounding sediment and also reveal the preservation of melanosome-like microbodies in the fossil. Carbon gradient along a depth profile and co-occurrence of carbon and sulphur are shown in the fossil by elastic backscattering (EBS) and particle-induced x-ray emission (PIXE), which are promising techniques for the elemental analysis of fossil soft tissues. The molecular composition of modern and fossil soft tissues was assessed from micro-attenuated total reflectance fourier transform infrared spectroscopy (micro-ATR FTIR), solid-state 13C nuclear magnetic resonance (CP-MAS 13C NMR) and pyrolysis gas chromatography mass spectrometry in the presence of TMAH (TMAH-Py-GC-MS). Results indicate that the proteinaceous material that comprises the modern feathers is not present in the fossil feathers. The fossil feathers and the embedding sediment exhibit a highly aliphatic character. However, substantial differences exist between these samples, revealing that the organic matter of the fossil feathers is, at least partially, derived from original constituents of the feathers. Our results suggest that, despite the morphological preservation of Anchiornis feathers, original proteins, that is keratin, were probably not preserved in the 160-myr-old feathers. 相似文献
139.
Sen Wang Fei Zheng Meijing Zhang Jun Tu Yanping Chen Jianhua Yuan Qingchang Meng 《Phyton》2020,89(4):861-871
Endosperm mutants are critical to the studies on both starch synthesis
and metabolism and genetic improvement of starch quality in maize. In the present study, a novel maize endosperm mutant A0178 of natural variation was used
as the experimental material and identified and then characterized. Through phenotypic identification, genetic analysis, main ingredients measurement and
embryo rescue, development of genetic mapping population from A0178, the
endosperm mutant gene was located. The results showed that the mutant exhibited
extremely low germination ability as attributed to the inhibited embryo development, and amounts of sugars were accumulated in the mutant seeds and more
sugars content was detected at 23 days after pollination (DAP) in A0178 than
B73. Employing genetic linkage analysis, the mutant trait was mapped in the
bin 5.04 on chromosome 5. Sequence analysis showed that two sites of base transversion and insertion presented in the protein coding region and non-coding
region of the mutant brittle-1 (bt1), the adenylate translocator encoding gene
involved in the starch synthesis. The single base insertion in the coding region
cause frameshift mutation, early termination and lose of function of Brittle-1
(BT1). All results suggested that bt1 is a novel allelic gene and the causal gene
of this endosperm mutant, providing insights on the mechanism of endosperm formation in maize. 相似文献
140.
Radiation and Environmental Biophysics - Objective of the present study was to investigate the tolerant radiation dose of nasal mucosa by observing and analyzing patients who received... 相似文献