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101.
Jiangying Cao Jie Zang Xiujie Kong Chunlong Zhao Ting Chen Yingying Ran Hang Dong Wenfang Xu Yingjie Zhang 《Bioorganic & medicinal chemistry》2019,27(6):978-990
Aminopeptidase N (APN) has been proved to be deeply associated with cancer angiogenesis, metastasis and invasion. Therefore, APN gains increasing attention as a promising anti-tumor target. In the current study, we report the design, synthesis, biological evaluation and structure-activity relationship of one new series of leucine ureido derivatives containing the 1,2,3-triazole moiety. Among them, compound 31f was identified as the best APN inhibitor with IC50 value being two orders of magnitude lower than that of the positive control bestatin. Compound 31f possessed selective cytotoxicity to several tumor cell lines over the normal cell line human umbilical vein endothelial cells (HUVECs). Notably, when combined with 5-fluorouracil (5-Fu), 31f exhibited synergistic anti-proliferation effect against several tumor cell lines. At the same concentration, 31f exhibited much better anti-angiogenesis activities than bestatin in the HUVECs capillary tube formation assay and the rat thoracic aorta rings test. In the in vitro anti-invasion assay, 31f also exhibited superior potency over bestatin. Moreover, considerable in vivo antitumor potencies of 31f alone or in combination with 5-Fu were observed without significant toxic signs in a mouse heptoma H22 tumor transplant model. 相似文献
102.
Liu Jing Chen Yunfu Li Long Yang Endong Wang Yansheng Wu Hang Zhang Lixin Wang Weiyun Zhang Buchang 《Journal of industrial microbiology & biotechnology》2019,46(7):1013-1024
Journal of Industrial Microbiology & Biotechnology - In this work, we found that the Lrp/AsnC family protein SACE_5717 negatively regulated erythromycin biosynthesis in S. erythraea. Disruption... 相似文献
103.
近年来,分子标记和显微光学成像技术的系列突破,使得单细胞分辨的全脑尺度神经群落成像成为现实.然而,现有神经元形态重建工具的发展速度远远滞后于海量数据的产生速度,难以满足现阶段成像数据的分析需求.在此背景下,我们首先分析了神经元形态重建工具发展滞后的原因,简述现有半自动和全自动神经元形态重建工具的特点和最新发展,并结合现有工具的特点分析其向高通量、高准确度重建工具发展时面临的挑战.最后,我们对未来形态重建工具的发展趋势及应用前景做出展望. 相似文献
104.
林分因子对云顶山不同人工林林下植物多样性的影响 总被引:1,自引:0,他引:1
该研究采用典型抽样法,以成都云顶山5种人工林——柏木 枫杨林(BF)、银杏 楠木林(YN)、光皮梾木 香樟林(GZ)、枫杨 桤木林(FQ)、柏木林(CB)为研究对象,分析不同人工林的林下植物组成与多样性特征,并确定影响林下植物多样性的主导林分因子,为当地人工林经营管理提供理论依据。结果表明:(1)研究区共记录林下植物168种,隶属于62科130属;5种人工林灌木层与草本层的科属种数均以GZ最多。(2)5种不同人工林灌木层与草本层的优势种数分别为7、4、7、6、4种和5、4、9、9、10种,数量都较少。(3)5种人工林的Shannon Wiener多样性指数(H)、Simpson优势度指数(H′)、物种丰富度指数(D)、Pielou均匀度指数(Jsw) 均基本表现为草本层>灌木层,BF、GZ灌木层的D略高;灌木层的H、H′、D值均以GZ最大,但不同人工林的Jsw差异不显著;草本层的H、H′、D、Jsw均基本呈现CB>FQ>GZ>BF>YN趋势,GZ的D值略高于FQ。(4)6个林分因子对灌木层4个物种多样性指数的影响均无显著差异;林分平均树高、平均枝下高、平均胸径、平均冠幅和林分密度是影响草本层H、D的主要因子,但各林分因子对草本层H′、Jsw的影响差异不显著。研究认为,林分结构对林下草本层物种多样性的影响更大,平均树高、平均枝下高、平均胸径、平均冠幅、林分密度对草本层多样性有显著影响。 相似文献
105.
106.
为了解决黑果枸杞中花青素稳定性问题,本文采用Box-Behnken设计对黑果枸杞提取物泡腾片配方进行优化,并对其进行质量评价。采用酸碱混合制粒压片法,通过单因素实验,筛选出片剂所需的辅料:崩解剂、填充剂、润滑剂以及甜味剂。采用响应面试验,结合感官评价进行处方优化,从而确定最优配方:柠檬酸32%、黑果枸杞提取物25%、碳酸氢钠24%、乳糖15%、甜蜜素3%、聚乙二醇6000 1%;对最优配方进行质量评价,各项指标均符合规定,其中花青素含量为8.06 mg/g。该泡腾片表面光滑,泡腾效果好,具有黑果枸杞香气,为实际生产提供理论依据。 相似文献
107.
Su Ya-ting Liu Chun Long Zhu Ren Hang Guo Xiao-hua 《Probiotics and antimicrobial proteins》2019,11(3):921-930
Probiotics and Antimicrobial Proteins - A dipicolonic acid fluorimetry assay was used instead of plate counting for the assessment of spore yields for enhanced optimization efficiency. The... 相似文献
108.
Linda Hoshan Rubin Jiang Joseph Moroney Ashley Bui Xiaolin Zhang Ta-Chun Hang Sen Xu 《Biotechnology progress》2019,35(1):e2743
pH control is critical in bioreactor operations, typically realized through a two-sided control loop, where CO2 sparging and base addition are used in bicarbonate-buffered media. Though a common approach, base addition could compromise culture performance due to the potential impact from pH excursions and osmolality increase in large-scale bioreactors. In this study, the feasibility of utilizing control of sparge gas composition as part of the pH control loop was assessed in Chinese hamster ovary (CHO) fed-batch cultures. Fine pH control was evaluated in multiple processes at different setpoints in small-scale ambr®250 bioreactors. Desired culture pH setpoints were successfully maintained via air sparge feedback control. As part of the pH control loop, air sparging was increased to improve CO2 removal automatically, hence increase culture pH, and vice versa. The effectiveness of this pH control strategy was seamlessly transferred from ambr®250 to 200 L scale, demonstrating scalability of the proposed methodology. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2743, 2019 相似文献
109.
The environmental carcinogen glycidaldehyde (GDA) and therapeutic chloroethylnitrosoureas (CNUs) can form hydroxymethyl etheno and ring-saturated ethano bases, respectively. The mutagenic potential of these adducts relies on their miscoding properties and repair efficiency. In this work, the ability of human thymine-DNA glycosylase (TDG) to excise 8-(hydroxymethyl)-3,N(4)-ethenocytosine (8-hm-varepsilonC) and 3,N(4)-ethanocytosine (EC) was investigated and compared with varepsilonC, a known substrate for TDG. When tested using defined oligonucleotides containing a single adduct, TDG is able to excise 8-hm-varepsilonC but not EC. The 8-hm-varepsilonC activity mainly depends on guanine pairing with the adduct. TDG removes 8-hm-varepsilonC less efficiently than varepsilonC but its activity can be significantly enhanced by human AP endonuclease 1 (APE1), a downstream enzyme in the base excision repair. TDG did not show any detectable activity toward EC when placed in various neighboring sequences, including the 5'-CpG site. Molecular modeling revealed a possible steric clash between the non-planar EC exocyclic ring and residue Asn 191 within the TDG active site, which could account for the lack of TDG activity toward EC. TDG was not active against the bulkier exocyclic adduct 3,N(4)-benzethenocytosine, nor the two adenine derivatives with same modifications as the cytosine derivatives, 7-hm-varepsilonA and EA. These findings expand the TDG substrate range and aid in understanding the structural requirements for TDG substrate specificity. 相似文献
110.
A large number of studies indicate that oxidative modification of plasma lipoproteins, especially low-density lipoprotein (LDL), is a critical factor in initiation and progression of atherosclerosis. We have previously found that ibuprofen (IBP), a potential antioxidant drug to inhibit LDL oxidation, interacted with lipoproteins in intact human plasma. In the present study, we compare the binding affinities of IBP to LDL and HDL (high-density lipoprotein) by (1)H NMR spectroscopy. When IBP is added into the HDL and LDL samples, the - N(+)(CH(3))(3) moieties of phosphatidylcholine (PC) and sphingomyelin (SM) in lipoprotein particles experience the chemical shift up-field drift. Intermolecular cross-peaks observed in NOESY spectra imply that there are direct interactions between ibuprofen and lipoproteins at both hydrophobic and hydrophilic (ionic) regions. These interactions are likely to be important in the solubility of ibuprofen into lipoprotein particles. Ibuprofen has higher impact on the PC and SM head group ( - N(+)(CH(3))(3)) and - (CH(2))(n) - group in HDL than that in LDL. This could be explained by either IBP has higher binding affinity to HDL than to LDL, or IBP induces orientation of the phospholipid head group at the surface of the lipoprotein particles. 相似文献