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51.
Matthew A.J. Duncton Eugene L. Piatnitski Chekler Reeti Katoch-Rouse Dan Sherman Wai C. Wong Leon M. Smith Joel K. Kawakami Alexander S. Kiselyov Daniel L. Milligan Chris Balagtas Yaron R. Hadari Ying Wang Sheetal N. Patel Robin L. Rolster James R. Tonra David Surguladze Stan Mitelman Paul Kussie Peter Bohlen Jacqueline F. Doody 《Bioorganic & medicinal chemistry》2009,17(2):731-740
A series of arylphthalazine derivatives were synthesized and evaluated as antagonists of VEGF receptor II (VEGFR-2). IM-094482 57, which was prepared in two steps from commercially available starting materials, was found to be a potent inhibitor of VEGFR-2 in enzymatic, cellular and mitogenic assays (comparable activity to ZD-6474). Additionally, 57 inhibited the related receptor, VEGF receptor I (VEGFR-1), and showed excellent exposure when dosed orally to female CD-1 mice. 相似文献
52.
53.
STAT6 ASODN对哮喘小鼠脾淋巴细胞影响的实验研究 总被引:1,自引:0,他引:1
目的研究STAT6反义寡核苷酸对哮喘小鼠脾淋巴细胞的影响作用。方法实验细胞分组:正常鼠空白组(A组)、正常鼠OVA组(B组)、哮喘空白组(C组)、哮喘OVA组(D组)、哮喘治疗组(E组)。正常设计并人工合成一段互补于小鼠STAT6 mRNA翻译起始区271-290的反义寡核苷酸片段,全链硫代修饰。用卵白蛋白和氢氧化铝复制哮喘模型,用淋巴细胞分离液分离脾淋巴细胞,进行体外培养并导入由阳离子脂质体转染剂Geneshuttle携带的反义寡核苷酸,观察反义寡核苷酸的转染对脾淋巴细胞STAT6蛋白表达水平及细胞培养上清中IL-4分泌水平的影响。免疫细胞化学观察脾淋巴细胞中STAT6蛋白的表达水平,同时采用酶联免疫吸附(ELISA)法测定脾细胞培养上清液中IL-4的浓度。结果D组细胞STAT6蛋白表达明显高于其余各组,均具有显著性差异(P均<0.01),STAT6 ASODN转染后,E组细胞该蛋白的表达量明显下降(P<0.01);D组脾淋巴细胞培养上清中IL-4分泌水平明显高于其余各组,均具有显著性差异(P均<0.01);STAT6 ASODN转染后,E组培养上清中IL-4分泌水平显著低于D组(P<0.01)。结论STAT6 ASODN可特异性抑制哮喘鼠脾淋巴细胞中STAT6蛋白的表达,并可特异性抑制脾淋巴细胞中IL-4的分泌,为反义基因技术治疗哮喘提供了依据。 相似文献
54.
Xiao‐Yan Xu Zhong‐Jie Ding Lei Chen Jin‐Ying Yan Gui‐Xin Li Shao‐Jian Zheng 《植物学报(英文版)》2015,57(10):848-858
Cadmium (Cd) is one of the most toxic elements and can be accumulated in plants easily; meanwhile, eIF5A is a highly conserved protein in all eukaryotic organisms. The present work tried to investigate whether eIF5A is involved in Cd accumulation and sensitivity in Arabidopsis (Arabidopsis thaliana L.) by comparing the wild‐type Columbia‐0 (Col‐0) with a knockdown mutant of AteIF5A‐2, fbr12‐3 under Cd stress conditions. The results showed that the mutant fbr12‐3 accumulated more Cd in roots and shoots and had significantly lower chlorophyll content, shorter root length, and smaller biomass, suggesting that downregulation of AteIF5A‐2 makes the mutant more Cd sensitive. Real‐time polymerase chain reaction revealed that the expressions of metal transporters involved in Cd uptake and translocation including IRT1, ZIP1, AtNramp3, and AtHMA4 were significantly increased but the expressions of PCS1 and PCS2 related to Cd detoxification were decreased notably in fbr12‐3 compared with Col‐0. As a result, an increase in MDA and H2O2 content but decrease in root trolox, glutathione and proline content under Cd stress was observed, indicating that a severer oxidative stress occurs in the mutant. All these results demonstrated for the first time that AteIF5A influences Cd sensitivity by affecting Cd uptake, accumulation, and detoxification in Arabidopsis. 相似文献
55.
Zhou HL Yang HJ Li YM Wang Y Yan L Guo XL Ba YC Liu S Wang TH 《Neurochemical research》2008,33(5):927-937
Limited information is available regarding the role of endogenous Glial cell line-derived neurotrophic factor (GDNF) in the
spinal cord following transection injury. The present study investigated the possible role of GDNF in injured spinal cords
following transection injury (T9–T10) in adult rats. The locomotor function recovery of animals by the BBB (Basso, Beattie, Bresnahan) scale score showed that
hindlimb support and stepping function increased gradually from 7 days post operation (dpo) to 21 dpo. However, the locomotion
function in the hindlimbs decreased effectively in GDNF-antibody treated rats. GDNF immunoreactivty in neurons in the ventral
horn of the rostral stump was stained strongly at 3 and 7 dpo, and in the caudal stump at 14 dpo, while immunostaining in
astrocytes was also seen at all time-points after transection injury. Western blot showed that the level of GDNF protein underwent
a rapid decrease at 7 dpo in both stumps, and was followed by a partial recovery at a later time-point, when compared with
the sham-operated group. GDNF mRNA-positive signals were detected in neurons of the ventral horn, especially in lamina IX.
No regenerative fibers from corticospinal tract can be seen in the caudal segment near the injury site using BDA tracing technique.
No somatosensory evoked potentials (SEP) could be recorded throughout the experimental period as well. These findings suggested
that intrinsic GDNF in the spinal cord could play an essential role in neuroplasticity. The mechanism may be that GDNF is
involved in the regulation of local circuitry in transected spinal cords of adult rats. 相似文献
56.
Kjetil Taskn Rigmor Solberg Ying Zhao Vidar Hansson Tore Jahnsen Michael J. Siciliano 《Genomics》1996,36(3):535
We have determined the chromosomal localization of the gene for the catalytic subunit Cα of cAMP-dependent protein kinase (locus PRKACA) to human chromosome 19 using polymerase chain reaction (PCR) and Southern blot analysis of two different somatic cell hybrid mapping panels. In addition, PCR analysis of a chromosome 19 mapping panel revealed the presence of a human Cα-specific amplification product only in cell lines containing the region 19p13.1 to 19q12. Finally, two-color fluorescencein situhybridization to metaphase chromosomes using the human Cα cDNA and human chromosome 19 inter-Alu-PCR product as probes localized the human Cα gene to chromosome region 19p13.1. 相似文献
57.
AAS法测定陕产不同生长期女贞子中铁含量 总被引:1,自引:0,他引:1
目的:对陕西境内不同产地、不同生长期女贞子中Fe含量进行分析测定.方法:采收陕西境内关中3市(渭南、西安、宝鸡)与陕南2市(安康、汉中)10月产女贞子;并采收西安8、9、10、11和12月产女贞子,去杂质阴干,室温密闭贮藏.样品湿法消解以后,采用火焰原子吸收光谱法检测其中的Fe含量,考察了干扰情况、方法的准确度和精密度.结果:本方法的检出限均小于0.3μg·mL-1,RSD≤2.46%,加样回收率在97.6~103.8%范围内.实际检测结果显示女贞子中铁含量较为丰富.结论:女贞子在不同产地、不同生长期铁含量不同,故在实际应用时应根据实际药用需要适时采集. 相似文献
58.
2009年3~6月,采用样方法对四川省洪雅县人工林赤腹松鼠危害相关的生境因子进行了调查。共设置了240个样方。样方调查中记录了2个反应危害等级的变量(危害株数和乔木总数)和11个生境变量(森林类型、海拔、坡向、坡度、坡位、距最近道路距离、距最近水源距离、乔木均高、乔木平均胸围、灌木盖度和草本盖度)。通过广义线性模型研究这些因子与人工林赤腹松鼠危害程度的关系。结果显示,赤腹松鼠危害程度与森林类型、坡度、坡向、乔木平均胸围呈显著性相关,与其他因子无显著相关性,在柳杉-杉木林中的危害高于纯柳杉林,在阴坡的危害低于其他坡向,危害程度随坡度和乔木平均胸围的增加而增加。 相似文献
59.
60.
Super-paramagnetic microbeads are widely used for cell isolation. Evaluation of the binding affinity of microbeads to cells using optical microscopy has been limited by its small scope. Here, magnetic property of microbeads was first investigated by using synchrotron radiation (SR) in-line x-ray phase contrast imaging (PCI). The cell line mouse LLC (Lewis lung carcinoma) was selected for cell adhesion studies. Targeted microbeads were prepared by attaching anti-VEGFR2 (vascular endothelial growth factor receptor-2) antibody to the shell of the microbeads. The bound microbeads were found to better adhere to LLC cells than unbound ones. PCI dynamically and clearly showed the magnetization and demagnetization of microbeads in PE-50 tube. The cells incubated with different types of microbeads were imaged by PCI, which provided clear and real-time visualization of the cell isolation. Therefore, PCI might be considered as a novel and efficient tool for further cell isolation studies. 相似文献