全文获取类型
收费全文 | 9362篇 |
免费 | 761篇 |
国内免费 | 673篇 |
专业分类
10796篇 |
出版年
2024年 | 28篇 |
2023年 | 127篇 |
2022年 | 287篇 |
2021年 | 494篇 |
2020年 | 337篇 |
2019年 | 387篇 |
2018年 | 428篇 |
2017年 | 273篇 |
2016年 | 399篇 |
2015年 | 587篇 |
2014年 | 659篇 |
2013年 | 654篇 |
2012年 | 848篇 |
2011年 | 782篇 |
2010年 | 436篇 |
2009年 | 383篇 |
2008年 | 466篇 |
2007年 | 372篇 |
2006年 | 349篇 |
2005年 | 298篇 |
2004年 | 236篇 |
2003年 | 183篇 |
2002年 | 178篇 |
2001年 | 179篇 |
2000年 | 154篇 |
1999年 | 168篇 |
1998年 | 79篇 |
1997年 | 83篇 |
1996年 | 74篇 |
1995年 | 89篇 |
1994年 | 87篇 |
1993年 | 58篇 |
1992年 | 87篇 |
1991年 | 77篇 |
1990年 | 68篇 |
1989年 | 44篇 |
1988年 | 55篇 |
1987年 | 36篇 |
1986年 | 42篇 |
1985年 | 53篇 |
1984年 | 26篇 |
1983年 | 17篇 |
1982年 | 21篇 |
1981年 | 11篇 |
1979年 | 11篇 |
1978年 | 14篇 |
1977年 | 10篇 |
1974年 | 11篇 |
1969年 | 5篇 |
1968年 | 8篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
51.
Iron-molybdenum cofactor from nitrogenase. Modified extraction methods as probes for composition 总被引:7,自引:0,他引:7
S S Yang W H Pan G D Friesen B K Burgess J L Corbin E I Stiefel W E Newton 《The Journal of biological chemistry》1982,257(14):8042-8048
Five modifications of the preparative procedure for isolating iron-molybdenum cofactor (FeMoco) from the molybdenum-iron (MoFe) protein of Azotobacter vinelandii nitrogenase have been developed. This variety of isolation methods has established that no single component of the original isolation protocol, i.e. Tris, Cl-, citrate, HPO4(2-), N,N-dimethylformamide, and N-methylformamide, is essential for the effective isolation and/or structural stability of FeMoco, although any of them may act as ligands to FeMoco when present. The acid-bse status (effective pH) of the extracting solvent is a key adjustable parameter in the isolation procedure. The new procedures produced FeMoco with yields, metal analysis, charge, EPR spectrum, and specific activity (after reconstituting crude extracts from A. vinelandii UW45 mutant cells) essentially identical with FeMoco isolated by the original procedure. After purification, FeMoco apparently contains molybdenum, iron, and sulfide in a 1:7:4 ratio with N-methylformamide as a ligand but no amino acid residues, common sugars, coenzyme A, or lipoic acid. Reaction with o-phenanthroline allows quantitation of both adventitious and FeMoco-associated iron. Correlations of total activity after UW45 reconstitution with molybdenum, total iron, and o-phenanthroline-resistant iron contents show that only the last gives a consistent relationship of 35 +/- 5 nmol of C2H4/min/ng atom of Fe. Both o-phenanthroline and EDTA interact with FeMoco to abolish its EPR signal in reactions reversible by additions of Fe2+ or Zn2+, respectively. These and related reactions point against the presence of an endogenous organic component in FeMoco and toward the presence of exogenous ligands and imply a relatively labile coordination sphere whose nature may be determinable by a systematic investigation. 相似文献
52.
NH2OH-treated, non-water-splitting chloroplasts can oxidize H2O2 to O2 through Photosystem II at substantial rates (100--250 muequiv . h-1 . mg-1 chlorophyll with 5 mM H2O2) using 2,5-dimethyl-p-benzoquinone as an electron acceptor in the presence of the plastoquinone antagonist dibromothymoquinone. This H2O2 leads to Photosystem II leads to dimethylquinone reaction supports phosphorylation with a P/e2 ratio of 0.25--0.35 and proton uptake with H+/e values of 0.67 (pH 8)--0.85 (pH 6). These are close to the P/e2 value of 0.3--0.38 and the H+/e values of 0.7--0.93 found in parallel experiments for the H2O leads to Photosystem II leads to dimethylquinone reaction in untreated chloroplasts. Semi-quantitative data are also presented which show that the donor leads to Photosystem II leads to dibromothymoquinone (leads to O2) reaction can support phosphorylation when the donor used is a proton-releasing reductant (benzidine, catechol) but not when it is a non-proton carrier (I-, ferrocyanide). 相似文献
53.
Bingqing Xia Xurui Shen Yang He Xiaoyan Pan Feng-Liang Liu Yi Wang Feipu Yang Sui Fang Yan Wu Zilei Duan Xiaoli Zuo Zhuqing Xie Xiangrui Jiang Ling Xu Hao Chi Shuangqu Li Qian Meng Hu Zhou Yubo Zhou Xi Cheng Xiaoming Xin Lin Jin Hai-Lin Zhang Dan-Dan Yu Ming-Hua Li Xiao-Li Feng Jiekai Chen Hualiang Jiang Gengfu Xiao Yong-Tang Zheng Lei-Ke Zhang Jingshan Shen Jia Li Zhaobing Gao 《Cell research》2021,31(8):847-860
Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.Subject terms: Cell death, Molecular biology 相似文献
54.
55.
Jianping Hu Yiting Zhang Shenglan Yi Chaokui Wang Xinyue Huang Su Pan Jinglu Yang Gangxiang Yuan Sisi Tan Hong Li 《International journal of biological sciences》2022,18(11):4545
Dendritic cells (DCs) are the major antigen-presenting cells and play an important role in autoimmune uveitis. Emerging evidence suggests that bile acids (BAs) regulate DCs maturation. However, the underlying mechanisms by which BAs regulate the function of DCs still need to be clarified. Here, we demonstrate that lithocholic acid (LCA) inhibits the production of pro-inflammatory cytokines and the expression of surface molecules in bone marrow-derived dendritic cells (BMDCs). LCA attenuates the severity of EAU by modulating the maturation of splenic CD11C+MHCIIhigh DCs. Notably, Takeda G-protein coupled receptor 5 (TGR5) deficiency partially reverses the inhibitory effect of LCA on DCs in vitro and in vivo. TGR5 activation also downregulates the NF-κB and MAPK pathways by inhibiting glutathione production and inducing oxidative stress in DCs, which leads to apoptosis and autophagy in DCs. In addition, LCA or INT-777 treatment increases the TGR5 expression in monocyte-derived dendritic cells (MD-DCs) of patients with active BD, whereas both LCA and TGR5 agonists inhibit the activation of MD-DCs. These results suggest that LCA and TGR5 agonists might be potential therapeutic drugs for the treatment of autoimmune uveitis. 相似文献
56.
57.
Ennian Li Kai Wang Bei Zhang Siqi Guo Senhao Xiao Qi Pan Xiaowan Wang Weiying Chen Yunshan Wu Hesong Xu Xiangqian Kong Cheng Luo Shijie Chen Bo Liu 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):1537
The DNA methyltransferases (DNMTs) were found in mammals to maintain DNA methylation. Among them, DNMT1 was the first identified, and it is an attractive target for tumour chemotherapy. DC_05 and DC_517 have been reported in our previous work, which is non-nucleoside DNMT1 inhibitor with low micromolar IC50 values and significant selectivity towards other S-adenosyl-L-methionine (SAM)-dependent protein methyltransferases. In this study, through a process of similarity-based analog searching, a series of DNMT1 inhibitors were designed, synthesized, and evaluated as anticancer agents. SAR studies were conducted based on enzymatic assays. And most of the compounds showed strong inhibitory activity on human DNMT1, especially WK-23 displayed a good inhibitory effect on human DNMT1 with an IC50 value of 5.0 µM. Importantly, the pharmacokinetic (PK) profile of WK-23 was obtained with quite satisfying oral bioavailability and elimination half-life. Taken together, WK-23 is worth developing as DNMT1-selective therapy for the treatment of malignant tumour. 相似文献
58.
A new technique to expand human mesenchymal stem cells using basement membrane extracellular matrix 总被引:11,自引:0,他引:11
Matsubara T Tsutsumi S Pan H Hiraoka H Oda R Nishimura M Kawaguchi H Nakamura K Kato Y 《Biochemical and biophysical research communications》2004,313(3):503-508
Mesenchymal stem cells (MSC) show a very short proliferative life span and readily lose the differentiation potential in culture. However, the growth rate and the proliferative life span of the stem cells markedly increased using tissue culture dishes coated with a basement membrane-like extracellular matrix, which was produced by PYS-2 cells or primary endothelial cells. Furthermore, the stem cells expanded on the extracellular matrix, but not those on plastic tissue culture dishes, retained the osteogenic, chondrogenic, and adipogenic potential throughout many mitotic divisions. The extracellular matrix had greater effects on the proliferation of MSC and the maintenance of the multi-lineage differentiation potential than basic fibroblast growth factor. Mesenchymal stem cells expanded on the extracellular matrix should be useful for regeneration of large tissue defects and repeated cell therapies, which require a large number of stem or progenitor cells. 相似文献
59.
Many factors can affect the assembly of communities, ranging from species pools to habitat effects to interspecific interactions.
In microbial communities, the predominant focus has been on the well-touted ability of microbes to disperse and the environment
acting as a selective filter to determine which species are present. In this study, we investigated the role of biotic interactions
(e.g., competition, facilitation) in fungal endophyte community assembly by examining endophyte species co-occurrences within
communities using null models. We used recombinant inbred lines (genotypes) of maize (Zea mays) to examine community assembly at multiple habitat levels, at the individual plant and host genotype levels. Both culture-dependent
and culture-independent approaches were used to assess endophyte communities. Communities were analyzed using the complete
fungal operational taxonomic unit (OTU) dataset or only the dominant (most abundant) OTUs in order to ascertain whether species
co-occurrences were different for dominant members compared to when all members were included. In the culture-dependent approach,
we found that for both datasets, OTUs co-occurred on maize genotypes more frequently than expected under the null model of
random species co-occurrences. In the culture-independent approach, we found that OTUs negatively co-occurred at the individual
plant level but were not significantly different from random at the genotype level for either the dominant or complete datasets.
Our results showed that interspecific interactions can affect endophyte community assembly, but the effects can be complex
and depend on host habitat level. To our knowledge, this is the first study to examine endophyte community assembly in the
same host species at multiple habitat levels. Understanding the processes and mechanisms that shape microbial communities
will provide important insights into microbial community structure and the maintenance of microbial biodiversity. 相似文献
60.