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Neurochemical Research - Mounting evidences have demonstrated that diet-induced obesity is associated with cognition impairment via increasing oxidative stress and inflammation in the brain.... 相似文献
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Xiaodi Niu Yawen Gao Yiding Yu Yanan Yang Guizhen Wang Lin Sun 《Journal of biomolecular structure & dynamics》2019,37(5):1220-1230
Previous studies found that the activity of Sortase A, a bacterial surface protein from Staphylococcus aureus, was inhibited by curcumin and its analogues. To explore this inhibitory mechanism, Sortase A and its inhibitors in complex systems were studied by molecular docking, molecular modelling, binding energy decomposition calculation and steered molecular dynamics simulations. Energy decomposition analysis indicated that PRO-163, LEU-169, GLN-172, ILE-182 and ILE-199 are key residues in Sortase A-inhibitor complexes. Furthermore, interactions between the methoxyl group on the benzene ring in the conjugated molecule (curcumin, demethoxycurcumin, bisdemethoxycurcumin) and VAL-168, LEU-169 and GLN-172 induce the inhibitory activity based on the energy decomposition and distance analyses between the whole residues and inhibitors. However, because of its coiled structure, the non-conjugated molecule, tetrahydrocurcumin, with key residues in the binding sites of Sortase A, interacted weakly with SrtA, leading to the loss of inhibitory activity. Based on these results, the methoxyl group on the benzene ring in the conjugated molecule largely influenced the inhibitory activity of the Sortase A inhibitors. 相似文献
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Canyang Niu Xiaoying Sun Fang Hu Xiaowen Tang KeWei Wang 《The Journal of biological chemistry》2022,298(3)
Transient receptor potential vanilloid 3 (TRPV3), robustly expressed in the skin, is a nonselective calcium-permeable cation channel activated by warm temperature, voltage, and certain chemicals. Natural monoterpenoid carvacrol from plant oregano is a known skin sensitizer or allergen that specifically activates TRPV3 channel. However, how carvacrol activates TRPV3 mechanistically remains to be understood. Here, we describe the molecular determinants for chemical activation of TRPV3 by the agonist carvacrol. Patch clamp recordings reveal that carvacrol activates TRPV3 in a concentration-dependent manner, with an EC50 of 0.2 mM, by increasing the probability of single-channel open conformation. Molecular docking of carvacrol into cryo-EM structure of TRPV3 combined with site-directed mutagenesis further identified a unique binding pocket formed by the channel S2-S3 linker important for mediating this interaction. Within the binding pocket consisting of four residues (Ile505, Leu508, Arg509, and Asp512), we report that Leu508 is the most critical residue for the activation of TRPV3 by carvacrol, but not 2-APB, a widely used nonspecific agonist and TRP channel modulator. Our findings demonstrate a direct binding of carvacrol to TRPV3 by targeting the channel S2-S3 linker that serves as a critical domain for chemical-mediated activation of TRPV3. We also propose that carvacrol can function as a molecular tool in the design of novel specific TRPV3 modulators for the further understanding of TRPV3 channel pharmacology. 相似文献
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Yiwei Niu Xueyi Teng Honghong Zhou Yirong Shi Yanyan Li Yiheng Tang Peng Zhang Huaxia Luo Quan Kang Tao Xu Shunmin He 《Nucleic acids research》2022,50(5):2493
Mobile element insertions (MEIs) are a major class of structural variants (SVs) and have been linked to many human genetic disorders, including hemophilia, neurofibromatosis, and various cancers. However, human MEI resources from large-scale genome sequencing are still lacking compared to those for SNPs and SVs. Here, we report a comprehensive map of 36 699 non-reference MEIs constructed from 5675 genomes, comprising 2998 Chinese samples (∼26.2×, NyuWa) and 2677 samples from the 1000 Genomes Project (∼7.4×, 1KGP). We discovered that LINE-1 insertions were highly enriched in centromere regions, implying the role of chromosome context in retroelement insertion. After functional annotation, we estimated that MEIs are responsible for about 9.3% of all protein-truncating events per genome. Finally, we built a companion database named HMEID for public use. This resource represents the latest and largest genomewide study on MEIs and will have broad utility for exploration of human MEI findings. 相似文献
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Hade Ramos Anne Monette Meijuan Niu Aldo Barrera Brenda Lpez-Ulloa Yazmín Fuentes Paola Guizar Karla Pino Luc DesGroseillers Andrew
J Mouland Marcelo Lpez-Lastra 《Nucleic acids research》2022,50(1):411
Translation initiation of the viral genomic mRNA (vRNA) of human immunodeficiency virus-type 1 (HIV-1) can be mediated by a cap- or an internal ribosome entry site (IRES)-dependent mechanism. A previous report shows that Staufen1, a cellular double-stranded (ds) RNA-binding protein (RBP), binds to the 5’untranslated region (5′UTR) of the HIV-1 vRNA and promotes its cap-dependent translation. In this study, we now evaluate the role of Staufen1 as an HIV-1 IRES-transacting factor (ITAF). We first confirm that Staufen1 associates with both the HIV-1 vRNA and the Gag protein during HIV-1 replication. We found that in HIV-1-expressing cells, siRNA-mediated depletion of Staufen1 reduces HIV-1 vRNA translation. Using dual-luciferase bicistronic mRNAs, we show that the siRNA-mediated depletion and cDNA-mediated overexpression of Staufen1 acutely regulates HIV-1 IRES activity. Furthermore, we show that Staufen1-vRNA interaction is required for the enhancement of HIV-1 IRES activity. Interestingly, we find that only Staufen1 harboring an intact dsRNA-binding domain 3 (dsRBD3) rescues HIV-1 IRES activity in Staufen1 CRISPR-Cas9 gene edited cells. Finally, we show that the expression of Staufen1-dsRBD3 alone enhances HIV-1 IRES activity. This study provides evidence of a novel role for Staufen1 as an ITAF promoting HIV-1 vRNA IRES activity. 相似文献
200.
Sheng Niu Jia Wang Bin Bai Lili Wu Anqi Zheng Qian Chen Pei Du Pengcheng Han Yanfang Zhang Yunfei Jia Chengpeng Qiao Jianxun Qi Wenxia Tian HongWei Wang Qihui Wang George Fu Gao 《The EMBO journal》2022,41(1)
Correction to: The EMBO Journal (2021) 40: e107786. DOI 10.15252/embj.2021107786 | Published online 8 June 2021The authors would like to add three references to the paper: Starr et al and Zahradník et al also reported that the Q498H or Q498R mutation has enhanced binding affinity to ACE2; and Liu et al reported on the binding of bat coronavirus to ACE2.Starr et al and Zahradník et al have now been cited in the Discussion section, and the following sentence has been corrected from:“According to our data, the SARS‐CoV‐2 RBD with Q498H increases the binding strength to hACE2 by 5‐fold, suggesting the Q498H mutant is more ready to interact with human receptor than the wildtype and highlighting the necessity for more strict control of virus and virus‐infected animals”.to“Here, according to our data and two recently published papers, the SARS‐CoV‐2 RBD with Q498H or Q498R increases the binding strength to hACE2 (Starr et al, 2020; Zahradník et al, 2021), suggesting the mutant with Q498H or Q498R is more ready to interact with human receptor than the wild type and highlighting the necessity for more strict control of virus and virus‐infected animals”.The Liu et al citation has been added to the following sentence:“In another paper published by our group recently, RaTG13 RBD was found to bind to hACE2 with much lower binding affinity than SARS‐CoV‐2 though RaTG13 displays the highest whole‐genome sequence identity (96.2%) with the SARS‐CoV‐2 (Liu et al, 2021)”.Additionally, the authors have added the GISAID accession IDs to the sequence names of the SARS‐CoV‐2 in two human samples (Discussion section). To make identification unambiguous, the sequence names have been updated from “SA‐lsf‐27 and SA‐lsf‐37” to “GISAID accession ID: EPI_ISL_672581 and EPI_ISL_672589”.Lastly, the authors declare in the Materials and Methods section that all experiments employed SARS‐CoV‐2 pseudovirus in cultured cells. These experiments were performed in a BSL‐2‐level laboratory and approved by Science and Technology Conditions Platform Office, Institute of Microbiology, Chinese Academy of Sciences.These changes are herewith incorporated into the paper. 相似文献