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71.
Weiduan Xu Jianmin Chen Glenn Yamasaki John E. Murphy Baisong Mei 《Molecular biotechnology》2010,45(3):248-256
Many therapeutic proteins require appropriate glycosylation for their biological activities and plasma half life. Coagulation
factor VIII (FVIII) is a glycoprotein which has extensive post-translational modification by N-linked glycosylation. The terminal
sialic acid in the N-linked glycans of FVIII is required for maximal circulatory half life. The extent of FVIII sialylation
can be determined by high pH anion-exchange chromatography coupled with a pulse electrochemical detector (HPAEC-PED), but
this requires a large amount of purified protein. Using FVIII as a model, the objective of the present study was to develop
assays that enable detection and prediction of sialylation deficiency at an early stage in the process and thus prevent downstream
product quality excursions. Lectin ECA (Erythrina Cristagalli) binds to unsialylated Galβ1-4 GlcNAc and the ECA-binding level (i.e., terminal Gal(β1-4) exposure) is inversely proportional
to the level of sialylation. By using ECA, a cell-based assay was developed to measure the global sialylation profile in FVIII
producing cells. To examine the Galβ1-4 exposure on the FVIII molecule in bioreactor tissue culture fluid (TCF), an ELISA-based
ECA-FVIII binding assay was developed. The ECA-binding specificity in both assays was assessed by ECA-specific sugar inhibitors
and neuraminidase digestion. The ECA-binding specificity was also independently confirmed by a ST3GAL4 siRNA knockdown experiment.
To establish the correlation between Galβ1-4 exposure and the HPAEC-PED determined FVIII sialylation value, the FVIII containing
bioreactor TCF and the purified FVIII samples were tested with ECA ELISA binding assay. The results indicated an inverse correlation
between ECA binding and the corresponding HPAEC-PED sialylation value. The ECA-binding assays are cost effective and can be
rapidly performed, thereby making them effective for in-process monitoring of protein sialylation. 相似文献
72.
Autophagy induction by xanthoangelol exhibits anti‐metastatic activities in hepatocellular carcinoma
Xiuwei Yang Jing Xie Xiaoxiao Liu Zichao Li Kun Fang Luying Zhang Mei Han Zhuang Zhang Zhi Gong Xuezhu Lin Xianzhou Shi Hui Gao Kui Lu 《Cell biochemistry and function》2019,37(3):128-138
Xanthoangelol (XAG), a prenylated chalcone isolated from the Japanese herb Angelica keiskei Koidzumi, has been reported to exhibit antineoplastic properties. However, the specific anti‐tumor activity of XAG in human hepatocellular carcinoma (HCC), and the relevant mechanisms are not known. Herein, we evaluated the effect of XAG against HCC in vitro and in vivo. Although XAG treatment did not significantly reduce the viability of the Hep3B and Huh7 cell lines, it suppressed cell migration, invasion, and EMT. This anti‐metastatic effect of XAG was due to induction of autophagy, because treatment with the autophagy inhibitor 3‐methyadenine (3‐MA) or knockdown of the pro‐autophagy Beclin‐1 effectively abrogated the XAG‐induced suppression of metastasis. Mechanistically, XAG induced autophagy via activation of the AMPK/mTOR signaling pathway, and XAG treatment dramatically increased the expression of p‐AMPK while decreasing p‐mTOR expression. In addition, blocking AMPK/mTOR axis with compound C abrogated the autophagy‐mediated inhibition of metastasis. The murine model of HCC metastasis also showed that XAG effectively reduced the number of metastatic pulmonary nodules. Taken together, our results revealed that autophagy via the activation of AMPK/mTOR pathway is essential for the anti‐metastatic effect of XAG against HCC. These findings not only contribute to our understanding of the anti‐tumor activity of XAG but also provide a basis for its clinical application in HCC. Before this study, evidence of XAG on HCC was purely anecdotal; present study provides the first comprehensive assessments of XAG on HCC metastasis and investigates its underlying mechanism. Results suggest that XAG exerts anti‐metastatic properties against HCC through inducing autophagy which is mediated by the activation of AMPK/mTOR signaling pathway. This research extends our knowledge about the antineoplastic properties of XAG and suggests that induction autophagy may represent future treatment strategies for metastatic HCC. 相似文献
73.
N Mei 《Comptes rendus des séances de la Société de biologie et de ses filiales》1980,174(6):1010-1015
The peripheral effect of two analgesics (aspirin and dibencozide) was studied on anaesthetized cats. Several types of neurons and stimulations were performed in this work: traction for periodontal mechanoreceptors connected to small-sized trigeminal fibres, distension for the muscular intestinal mechanoreceptors connected to non-myelinated vagal fibres, chemical stimulation by means of phenyldiguanide for the non-myelinated vagal fibres, electrical stimulation of the myelinated and non-myelinated vagal fibres. In all cases, unitary activities were recorded into corresponding ganglia (nodose or gasserian) with extracellular glass microelectrodes. After injection of analgesics, a decrease of control responses were observed till 30 minutes but the maximum occurred between 1 and 5 minutes. This effect concerned the non-myelinated neurones as well as the myelinated ones. It can be explained by a direct action of analgesics on the ending excitability. 相似文献
74.
Bo‐Wen Gu Lian‐Mei Tan Cui‐Jun Zhang Xiao‐Mei Hou Xue‐Wei Cai She Chen Xin‐Jian He 《植物学报(英文版)》2020,62(11):1703-1716
Imitation Switch (ISWI) chromatin remodelers are known to function in diverse multi‐subunit complexes in yeast and animals. However, the constitution and function of ISWI complexes in Arabidopsis thaliana remain unclear. In this study, we identified forkhead‐associated domain 2 (FHA2) as a plant‐specific subunit of an ISWI chromatin‐remodeling complex in Arabidopsis. By in vivo and in vitro analyses, we demonstrated that FHA2 directly binds to RLT1 and RLT2, two redundant subunits of the ISWI complex in Arabidopsis. The stamen filament is shorter in the fha2 and rlt1/2 mutants than in the wild type, whereas their pistil lengths are comparable. The shorter filament, which is due to reduced cell size, results in insufficient pollination and reduced fertility. The rlt1/2 mutant shows an early‐flowering phenotype, whereas the phenotype is not shared by the fha2 mutant. Consistent with the functional specificity of FHA2, our RNA‐seq analysis indicated that the fha2 mutant affects a subset of RLT1/2‐regulated genes that does not include genes involved in the regulation of flowering time. This study demonstrates that FHA2 functions as a previously uncharacterized subunit of the Arabidopsis ISWI complex and is exclusively involved in regulating stamen development and plant fertility. 相似文献
75.
Munoz Frances M. Patel Priya A. Gao Xinghua Mei Yixiao Xia Jingsheng Gilels Sofia Hu Huijuan 《Purinergic signalling》2020,16(1):97-107
Purinergic Signalling - Astrocytes mediate a remarkable variety of cellular functions, including gliotransmitter release. Under pathological conditions, high concentrations of the purinergic... 相似文献
76.
Leon Wong Yu‐An Huang Zhu‐Hong You Zhan‐Heng Chen Mei‐Yuan Cao 《Journal of cellular and molecular medicine》2020,24(1):79-87
LncRNA and miRNA are key molecules in mechanism of competing endogenous RNAs(ceRNA), and their interactions have been discovered with important roles in gene regulation. As supplementary to the identification of lncRNA‐miRNA interactions from CLIP‐seq experiments, in silico prediction can select the most potential candidates for experimental validation. Although developing computational tool for predicting lncRNA‐miRNA interaction is of great importance for deciphering the ceRNA mechanism, little effort has been made towards this direction. In this paper, we propose an approach based on linear neighbour representation to predict lncRNA‐miRNA interactions (LNRLMI). Specifically, we first constructed a bipartite network by combining the known interaction network and similarities based on expression profiles of lncRNAs and miRNAs. Based on such a data integration, linear neighbour representation method was introduced to construct a prediction model. To evaluate the prediction performance of the proposed model, k‐fold cross validations were implemented. As a result, LNRLMI yielded the average AUCs of 0.8475 ± 0.0032, 0.8960 ± 0.0015 and 0.9069 ± 0.0014 on 2‐fold, 5‐fold and 10‐fold cross validation, respectively. A series of comparison experiments with other methods were also conducted, and the results showed that our method was feasible and effective to predict lncRNA‐miRNA interactions via a combination of different types of useful side information. It is anticipated that LNRLMI could be a useful tool for predicting non‐coding RNA regulation network that lncRNA and miRNA are involved in. 相似文献
77.
Xin Li Chen Huang Cheng Liang Sui Chun Mei Liang Guang Ying Qi Qian Yao Ren Jian Chen Zhao Quan Huang 《Journal of cellular and molecular medicine》2020,24(1):875-885
Formononetin is a natural isoflavone compound found mainly in Chinese herbal medicines such as astragalus and red clover. It is considered to be a typical phytooestrogen. In our previous experiments, it was found that formononetin has a two‐way regulatory effect on endothelial cells (ECs): low concentrations promote the proliferation of ECs and high concentrations have an inhibitory effect. To find a specific mechanism of action and provide a better clinical effect, we performed a structural transformation of formononetin and selected better medicinal properties for formononetin modifier J1 and J2 from a variety of modified constructs. The MTT assay measured the effects of drugs on human umbilical vein endothelial cell (HUVEC) activity. Scratch and transwell experiments validated the effects of the drugs on HUVEC migration and invasion. An in vivo assessment effect of the drugs on ovariectomized rats. Long‐chain non‐coding RNA for EWSAT1, which is abnormally highly expressed in HUVEC, was screened by gene chip, and the effect of the drug on its expression was detected by PCR after the drug was applied. The downstream factors and their pathways were analysed, and the changes in the protein levels after drug treatment were evaluated by Western blot. In conclusion, the mechanism of action of formononetin, J1 and J2 on ECs may be through EWSAT1‐TRAF6 and its downstream pathways. 相似文献
78.
79.
Chunhong Xi Yingduan Zhang Mei Yan Qing Lv Huan Lu Jun Zhou Yucheng Wang Jianbo Li 《Journal of cellular and molecular medicine》2020,24(17):10166-10176
Pathogenesis and treatment for diabetic neuropathy are still complex. A deficit of neurotrophic factors affecting Schwann cells is a very important cause of diabetic neuropathy. Neuritin is a newly discovered potential neurotrophic factor. In this study, we explored the effect of exogenous neuritin on survivability and functions of diabetic Schwann cells of rats with experimental diabetic neuropathy. Diabetic neuropathy was induced in rats. 12‐week diabetic rats contrasted with non‐diabetic normal rats had decreased levels of serum neuritin and slowed nerve conduction velocities (NCVs). Schwann cells isolated from these diabetic rats and cultured in high glucose showed reduced cell neuritin mRNA and protein and supernatant neuritin protein, increased apoptosis rates, increased caspase‐3 activities and progressively reduced viability. In contrast, exogenous neuritin treatment reduced apoptosis and improved viability, with elevated Bcl‐2 levels (not Bax) and decreased caspase‐3 activities. Co‐cultured with diabetic Schwann cells pre‐treated with exogenous neuritin in high glucose media, and diabetic DRG neurons showed lessened decreased neurite outgrowth and supernatant NGF concentration occurring in co‐culture of diabetic cells. Exogenous neuritin treatment ameliorated survivability and functions of diabetic Schwann cells of rats with diabetic neuropathy. Our study may provide a new mechanism and potential treatment for diabetic neuropathy. 相似文献
80.
Yan Du Mei‐ju Zhang Lan‐lan Li Xiao‐Lin Xu Hao Chen Yu‐bin Feng Yan Li Xiao‐qin Peng Fei‐hu Chen 《Journal of cellular and molecular medicine》2020,24(12):6952-6965
Acute myeloid leukaemia (AML) remains a therapeutic challenge and improvements in chemotherapy are needed. 4‐Amino‐2‐trifluoromethyl‐phenyl retinate (ATPR), a novel all‐trans retinoic acid (ATRA) derivative designed and synthesized by our team, has been proven to show superior anticancer effect compared with ATRA on various cancers. However, its potential effect on AML remains largely unknown. Lactate dehydrogenase B (LDHB) is the key glycolytic enzyme that catalyses the interconversion between pyruvate and lactate. Currently, little is known about the role of LDHB in AML. In this study, we found that ATPR showed antileukaemic effects with RARα dependent in AML cells. LDHB was aberrantly overexpressed in human AML peripheral blood mononuclear cell (PBMC) and AML cell lines. A lentiviral vector expressing LDHB‐targeting shRNA was constructed to generate a stable AML cells with low expression of LDHB. The effect of LDHB knockdown on differentiation and cycle arrest of AML cells was assessed in vitro and vivo, including involvement of Raf/MEK/ERK signalling. Finally, these data suggested that ATPR showed antileukaemic effects by RARα/LDHB/ ERK‐glycolysis signalling axis. Further studies should focus on the underlying leukaemia‐promoting mechanisms and investigate LDHB as a therapeutic target. 相似文献