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991.
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Zhen-hua Wang Xiao-han Cao Xiao-gang Du Hai-bo Feng Di-Wang He-Song Xian-yin Zeng 《Cellular immunology》2014
The purpose of the study was to construct mucosal vaccine of a recombinant Lactococcus lactis expressing PRRSV ORF6 gene and evaluate mucosal and systemic immune response against PRRSV in mice after intranasal immunization. The result show that the vaccine can stimulate mice to produce specific IgG in serum and remarkable special s-IgA in lung lavage fluid, at the same time, the contents of cytokines IL-2 and IFN-γ of the experimental group were significant higher than those of the control group (P < 0.01), however, the contents of cytokines IL-4 was not different to the all groups. In summary, the constructed mucosal vaccine can significantly induce mucosal immune, humoral immunity and cellular immunity involved Th1 type cytokines, which will lay a theoretical foundation on immune mechanism and new efficient vaccines for PRRSV. 相似文献
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Keng Po Lai Wai Fook Leong Jenny Fung Ling Chau Deyong Jia Li Zeng Huijuan Liu Lin He Aijun Hao Hongbing Zhang David Meek Chakradhar Velagapudi Samy L Habib Baojie Li 《The EMBO journal》2010,29(17):2994-3006
p53 mediates DNA damage‐induced cell‐cycle arrest, apoptosis, or senescence, and it is controlled by Mdm2, which mainly ubiquitinates p53 in the nucleus and promotes p53 nuclear export and degradation. By searching for the kinases responsible for Mdm2 S163 phosphorylation under genotoxic stress, we identified S6K1 as a multifaceted regulator of Mdm2. DNA damage activates mTOR‐S6K1 through p38α MAPK. The activated S6K1 forms a tighter complex with Mdm2, inhibits Mdm2‐mediated p53 ubiquitination, and promotes p53 induction, in addition to phosphorylating Mdm2 on S163. Deactivation of mTOR‐S6K1 signalling leads to Mdm2 nuclear translocation, which is facilitated by S163 phosphorylation, a reduction in p53 induction, and an alteration in p53‐dependent cell death. These findings thus establish mTOR‐S6K1 as a novel regulator of p53 in DNA damage response and likely in tumorigenesis. S6K1–Mdm2 interaction presents a route for cells to incorporate the metabolic/energy cues into DNA damage response and links the aging‐controlling Mdm2–p53 and mTOR‐S6K pathways. 相似文献
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Lu Y Jin X Chen Y Li S Yuan Y Mai G Tian B Long D Zhang J Zeng L Li Y Cheng J 《Cell biochemistry and function》2010,28(8):637-643
Hypoxia/reoxygenation (H/R)‐induced injury is the key factor associated with islet graft dysfunction. This study aims to examine the effect of mesenchymal stem cells (MSCs) on islet survival and insulin secretion under H/R conditions. Islets from rats were isolated, purified, cultured with or without MSCs, and exposed to hypoxia (O2 ≤ 1%) for 8 h and reoxygenation for 24 and 48 h, respectively. Islet function was evaluated by measuring basal and glucose‐stimulated insulin secretion (GSIS). Apoptotic islet cells were quantified using Annexin V‐FITC. Anti‐apoptotic effects were confirmed by mRNA expression analysis of hypoxia‐resistant molecules, HIF‐1α, HO‐1, and COX‐2, using semi‐quantitative retrieval polymerase chain reaction (RT‐PCR). Insulin expression in the implanted islets was detected by immunohistological analysis. The main results show that the stimulation index (SI) of GSIS was maintained at higher levels in islets co‐cultured with MSCs. The MSCs protected the islets from H/R‐induced injury by decreasing the apoptotic cell ratio and increasing HIF‐1α, HO‐1, and COX‐2 mRNA expression. Seven days after islet transplantation, insulin expression in the MSC‐islets group significantly differed from that of the islets‐alone group. We proposed that MSCs could promote anti‐apoptotic gene expression by enhancing their resistance to H/R‐induced apoptosis and dysfunction. This study provides an experimental basis for therapeutic strategies based on enhancing islet function. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
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Peng Liu Song Nie Bing Li Zhong-Qiang Yang Zhi-Mei Xu Jian Fei Chyuansheng Lin Rong Zeng Guo-Liang Xu 《Molecular and cellular biology》2010,30(17):4245-4253
Biological methylation is a fundamental enzymatic reaction for a variety of substrates in multiple cellular processes. Mammalian N6amt1 was thought to be a homologue of bacterial N6-adenine DNA methyltransferases, but its substrate specificity and physiological importance remain elusive. Here, we demonstrate that N6amt1 functions as a protein methyltransferase for the translation termination factor eRF1 in mammalian cells both in vitro and in vivo. Mass spectrometry analysis indicated that about 70% of the endogenous eRF1 is methylated at the glutamine residue of the conserved GGQ motif. To address the physiological significance of eRF1 methylation, we disrupted the N6amt1 gene in the mouse. Loss of N6amt1 led to early embryonic lethality. The postimplantation development of mutant embryos was impaired, resulting in degeneration around embryonic day 6.5. This is in contrast to what occurs in Escherichia coli and Saccharomyces cerevisiae, which can survive without the N6amt1 homologues. Thus, N6amt1 is the first glutamine-specific protein methyltransferase characterized in vivo in mammals and methylation of eRF1 by N6amt1 might be essential for the viability of early embryos.Nucleic acids, proteins, carbohydrates, and lipids, as well as a body of small molecules, are subject to methylation in a wide variety of biological contexts (3). The majority of methylation reactions are catalyzed by S-adenosylmethionine (AdoMet)-dependent methyltransferases (MTases). These enzymes ubiquitously exist in species from all three domains of life.Methylation of DNA occurs on one of two bases: cytosine or adenine (19). In prokaryotes, adenine methylation is as widespread as cytosine methylation. In contrast, eukaryotic genomes are devoid of adenine methylation or this type of methylation is too rare to be detected (23, 26). Intriguingly, two putative N6-adenine DNA MTases, named N6amt1 and N6amt2, are encoded in the mouse and human genomes. In addition to the conserved AdoMet-binding signature motif GXGXG and other sequence elements, they possess the NPPY motif characteristic of the N6-adenine or N4-cytosine DNA MTases in bacteria (6, 14). N6amt1 was thus proposed as an AdoMet-dependent DNA MTase, although no evidence had been provided that N6amt1 could methylate DNA (23).No functional clue for N6amt1 existed until two groups independently identified Escherichia coli HemK, distantly related to N6amt1, as a protein MTase for polypeptide release factors RF1 and RF2 (8, 17). The HemK gene was initially discovered in a genetic screen for heme biosynthesis mutants (18), although subsequent studies revealed no direct involvement in heme metabolism. The presence of an NPPY motif, thought to be restricted to members of the adenine and cytosine amino methyltransferases, led to the suggestion that HemK could be an AdoMet-dependent DNA MTase (2). However, a series of genetic and biochemical experiments finally revealed that HemK methylates the side-chain amide group of a glutamine residue in the universally conserved tripeptide motif GGQ of the two release factors in E. coli (8, 17). Methylation of the release factors ensures efficient translation termination and release of newly synthesized peptide from the ribosome (16). Similarly, the yeast HemK homologue, YDR140w (Mtq2p), was confirmed to methylate the eukaryotic release factor eRF1 on a corresponding glutamine residue (9, 22). More recently, the human homologue N6amt1 (HemK2) was reported to methylate release factor 1 (eRF1) in vitro (5).We initially sought to characterize the function of N6amt1 as a potential DNA adenine MTase. Interestingly, the human N6amt1 gene is located on chromosome 21q21.3, a critical region for Down syndrome (1, 20). In this study, we report the identification of murine N6amt1 as a glutamine-specific MTase of eRF1 both in vitro and in vivo. Mammalian eRF1, the only mammalian release factor, is indeed methylated at the glutamine residue of the GGQ motif. Inactivation of the N6amt1 gene by targeted disruption led to embryonic lethality in the mouse. These data confirm that N6amt1 functions as a protein MTase in mammals and indicate that modulation of the eRF1 activity by N6amt1-mediated glutamine methylation might be essential for embryo viability. 相似文献