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991.
Xingxing Ge Xicheng Liu Zhenzhen Tian Shujiao Chen Xinyu Liu Lihua Guo Peiwei Gong Baoping Ling Xiang‐Ai Yuan Zhe Liu 《应用有机金属化学》2019,33(11)
Four half‐sandwich rutheniumII (RuII) complexes with triphenylamine‐modifed dipyridine frameworks were synthesized and characterized. The cytotoxicity of target complexes toward A549 (lung cancer cells), HeLa (cervical cancer cells) and HepG2 (hepatoma cells) were obtained by the MTT assay, which were superior to cisplatin with the IC50 values changed from 2.4 ± 0.1 μM to 9.2 ± 2.7 μM. Meanwhile, complexes possess the ability of antimetastasis to cancer cells. RuII complexes could be transported by serum albumin, catalyze the conversion of NADH (the reduced state of nicotinamide‐adenine dinucleotide) to NAD+ and induce the accumulation of reactive oxygen species, which confirmed the antineoplastic mechanism of oxidation. RuII complexes could enter A549 cells followed by a non‐energy dependent cellular uptake mechanism, target lysosomes with the Pearson's colocalization coefficient of 0.75, lead to lysosomal damage, disturb the cell cycle (S phase), and eventually induce apoptosis. The results demonstrate that these RuII complexes are potential anticancer agents with dual functions, including metastasis inhibition and lysosomal damage. 相似文献
992.
Jianshuang Wang Michael Van Parys Lin Pan Yuan Chen Dorothy Cheung Janine McKnight Dennis Milanowski Xiao Ding Brian Dean 《Biomedical chromatography : BMC》2019,33(4)
A specific and robust LC–MS/MS method was developed and validated for the quantitative determination of GDC‐3280 in human plasma and urine. The nonspecific binding associated with urine samples was overcome by the addition of CHAPS. The sample volume was 25 μL for either matrix, and supported liquid extraction was employed for analyte extraction. d6‐GDC‐3280 was used as the internal standard. Linear standard curves (R2 > 0.9956) were established from 5.00 to 5000 ng/mL in both matrices with quantitation extended to 50,000 ng/mL through dilution. In plasma matrix, the precision (RSD) ranged from 1.5 to 9.9% (intra‐run) and from 2.4 to 7.2% (inter‐run); the accuracy (RE) ranged from 96.1 to 107% (intra‐run) and from 96.7 to 104% (inter‐run). Similarly, in urine the precision was 1.5–6.2% (intra‐run) and 1.9–6.1% (inter‐run); the accuracy was 83.1–99.3% (intra‐run) and 87.1–98.3% (inter‐run). Good recovery (>94%) and negligible matrix effect were achieved in both matrices. Long‐term matrix stability was established for at least 703 days in plasma and 477 days in urine. Bench‐top stability of 25 h and five freeze–thaw cycles were also confirmed in both matrices. The method was successfully implemented in GDC‐3280's first‐in‐human trial for assessing its pharmacokinetic profiles. 相似文献
993.
Ziwen Yuan Lijia Zhong Yongli Hua Peng Ji Wanling Yao Qi Ma Xiaosong Zhang Yanqiao Wen Lihong Yang Yanming Wei 《Biomedical chromatography : BMC》2019,33(4)
Angelica sinensis (Danggui, DG) parched with alcohol (Jiu Danggui, JDG) and charred DG are the main processed products of DG, which are used to treat blood stasis syndrome (BSS). However, their therapeutic effect and mechanisms are still unclear. Based on an acute rat BSS model, the intervention effects of DG and its processed products (DGPPs) were evaluated by the hemorheology and coagulation function parameters. Meanwhile, plasma and urine metabolites were detected and analyzed by liquid chromatography coupled to quadrupole time‐of‐flight mass spectrometry and multivariate statistical analysis method. The results of hemorheology, coagulation function parameters and metabolomics all showed that the BSS model was successfully established, DGPPs intervention could significantly relieve rats BSS and the therapeutic effect of JDG was best. Moreover, 23 differential metabolites (14 in plasma and nine in urine) were identified that were closely related to the BSS, involving seven potential target metabolic pathways. DGPP intervention showed different degrees of reverse effect on these metabolites. JDG was the most effective owing to extensive regulation effect on differential metabolites. This study provides a reference for understanding the pathological mechanism of BSS and the mechanism of DGPPs, which lays a theoretical foundation for the rational use of DGPPs in clinical practice. 相似文献
994.
Xiaomin Xu Xiaohong Ding Bo Yuan Weiwei Li Yimei Wang Yi Jin Haiyan Xu 《Biomedical chromatography : BMC》2019,33(6)
A rapid, simple and sensitive LC–MS/MS method was established and validated for simultaneous quantification of ticagrelor and its active metabolite AR‐C124910XX in human plasma. After plasma samples were deproteinized with acetonitrile, the post‐treatment samples were chromatographed on a Dikma C18 column interfaced with a triple quadrupole tandem mass spectrometer. Electrospray negative ionization mode and multiple reaction monitoring were adopted to assay ticagrelor and AR‐C124910XX. Acetonitrile and 5 mΜ ammonium acetate was used as the mobile phase with a gradient elution at a flow rate of 0.5 mL/min. The method was linear in the range of 0.781–800 ng/mL for both ticagrelor and AR‐C124910XX with a correlation coefficient ≥0.994. The intra‐ and inter‐day precisions were within 12.61% in terms of relative standard deviation and the accuracy was within ±7.88% in terms of relative error. The LC–MS/MS method was fully validated for its sensitivity, selectivity, stability, matrix effect and recovery. This convenient and specific LC–MS/MS method was successfully applied to the pharmacokinetic study of ticagrelor and AR‐C124910XX in healthy volunteers after an oral dose of 90 mg ticagrelor. 相似文献
995.
Yimei Wang Yi Qiao Xiaomin Xu Xiaohong Ding Weiwei Li Bo Yuan Haiyan Xu 《Biomedical chromatography : BMC》2019,33(8)
A sensitive and reliable LC–MS/MS method was developed and validated for simultaneous quantification of the major components of Huangqi–Honghua extact in rat plasma, including hydroxysafflor yellow A (HSYA), astragaloside IV (ASIV), calycosin‐7‐O‐β‐d ‐glucoside (CAG), calycosin, calycosin‐3′‐O‐glucuronide (C‐3′‐G) and calycosin‐3′‐O‐sulfate (C‐3′‐S). After extraction by protein precipitation with acetonitrile and methanol from plasma, the analytes were separated on a Hypersil BDS C18 column by gradient elution with acetonitrile and 5 mM ammonium acetate. The detection was carried out on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization source switched between negative and positive modes. HSYA was monitored in negative ionization mode from 0 to 4.9 min, and ASIV, CAG, calycosin, C‐3′‐G and C‐3′‐S were determined in positive ionization mode from 4.9 to 10 min. The lower limits of quantification of the analytes were 6.25 ng/mL for HSYA, 0.781 ng/mL for CAG and 1.56 ng/mL for ASIV and calycosin. The intra‐ and inter‐assay precision (RSD) values were within 13.43%, and accuracy (RE) ranged from ?8.75 to 9.92%. The validated method was then applied to the pharmacokinetic study of HSYA, ASIV, CAG, calycosin, C‐3′‐G and C‐3′‐S in rat after an oral administration of Huangqi–Honghua extract. 相似文献
996.
Qian Li Mingrui Yuan Jinyu Li Di Wei Shuangxi Mei Tao Cui Jingkun Wang Zhaoyun Zhu Xun Dong Jinfu Wan 《Magnetic resonance in chemistry : MRC》2019,57(11):934-938
Two new eudesmane derivatives, 1α,6β,9β-trihydroxy-eudesm-3-ene-1-O-β-d -glucopyranoside ( 1 ) and 1α,6β,9β-trihydroxy-eudesm-3-ene-1-(6-cinnamoyl)-O-β-d -glucopyranoside ( 2 ) were discovered from Merremia yunnanensis. The structures were elucidated by analysis of their spectroscopic data including HR-ESI-MS, 1D, and 2D NMR. It should be noted that this is the first report about structure elucidation and NMR assignment of compounds from M. yunnanensis. 相似文献
997.
采用薄层层析和氨基酸分析仪检测了细枝木麻黄弗兰克氏菌菌株Cc01的细胞化学组分.表明它的全细胞特征性糖为木糖和半乳糖;细胞壁氨基酸组分在薄层上只显示有赖氨酸.而无meso-DAP和甘氨酸;但在氨基酸分析仪上除含有谷氨酸(GLU)、甘氨酸(GLY)、丙氨酸(ALA)和二氨基庚二酸(DAP)以外,尚有较高含量的天冬氨酸(ASP)和赖氨酸(LYS).由这些氨基酸的分子比得出,菌株Cc01与胞壁Ⅱ型和Ⅲ型的参考菌株均明显不同,其特征性氨基酸分子比为Glu∶Gly∶Ala∶Dap∶Asp∶Lys为1.00∶0.13∶3.50∶0.21∶0.53∶0.78,其DAP含量仅为Ⅲ型菌株的1/6.表明Cc01的胞壁类型和其它弗兰克氏菌不一样,是一种特殊类型. 相似文献
998.
提出一种求解数值优化问题的演化算法--基于空间结构的演化算法(Space GA),在这种算法中,作者将演化种群中的每个个体放在固定的位置上,杂交操作在其邻居上的几个点进行,因此不用选择遗传操作的父体,从而避免了确定选择压力的问题,同时空间结构保证了搜索的全局性,遗传操作保证了较优解在其空间中的扩展,从而达到了全局寻优的目的。文章还讨论了不同的空间结构算法的影响,此算法可以求角数学规划问题、约束函数优化问题,如果对实型变量采用取整的操作,算法还可以求解混合整数非性规划问题,数值试验的结果表明了算法在求解的速度,稳定性,质量等方面都优于一般的演化算法。 相似文献
999.
袁玉仁 《南昌大学学报(理科版)》1989,13(3):1
本文探讨了在常规CMOS集成电路基础上设计三值逻辑电路的方法。从三值倒相器入手,结合常规CMOS门电路,给出了CMOS三值译码器的设计方案及应用电路。 相似文献
1000.
Yan Zhou Jinjian Li Han Yuan Rui Su Yue Huang Yiyou Huang Zhe Li Yinuo Wu Haibin Luo Chen Zhang Ling Huang 《Molecules (Basel, Switzerland)》2021,26(10)
Phosphodiesterase 2 (PDE2) has been regarded as a novel target for the treatment of Alzheimer’s disease (AD). In this study, we obtained (R)-LZ77 as a hit compound with moderate PDE2 inhibitory activity (IC50 = 261.3 nM) using a high-throughput virtual screening method based on molecular dynamics. Then, we designed and synthesized 28 dihydropyranopyrazole derivatives as PDE2 inhibitors. Among them, compound (+)-11h was the most potent PDE2 inhibitor, with an IC50 value of 41.5 nM. The molecular docking of PDE2-(+)-11h reveals that the 4-(trifluoromethyl)benzyl)oxyl side chain of the compound enters the H-pocket and forms strong hydrophobic interactions with L770/L809/F862, which improves inhibitory activity. The above results may provide insight for further structural optimization of highly potent PDE2 inhibitors and may lay the foundation for their use in the treatment of AD. 相似文献