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991.
Estrogen receptor α (ERα) plays critical roles in development and progression of breast cancer. Because ERα activity is strictly dependent upon the interaction with coregulators, coregulators are also believed to contribute to breast tumorigenesis. Cell Cycle and Apoptosis Regulator 1 (CCAR1) is an important co-activator for estrogen-induced gene expression and estrogen-dependent growth of breast cancer cells. Here, we identified Deleted in Breast Cancer 1 (DBC1) as a CCAR1 binding protein. DBC1 was recently shown to function as a negative regulator of the NAD-dependent protein deacetylase SIRT1. DBC1 associates directly with ERα and cooperates synergistically with CCAR1 to enhance ERα function. DBC1 is required for estrogen-induced expression of a subset of ERα target genes as well as breast cancer cell proliferation and for estrogen-induced recruitment of ERα to the target promoters in a gene-specific manner. The mechanism of DBC1 action involves inhibition of SIRT1 interaction with ERα and of SIRT1-mediated deacetylation of ERα. SIRT1 also represses the co-activator synergy between DBC1 and CCAR1 by binding to DBC1 and disrupting its interaction with CCAR1. Our results indicate that DBC1 and SIRT1 play reciprocal roles as major regulators of ERα activity, by regulating DNA binding by ERα and by regulating co-activator synergy. 相似文献
992.
Hydroxypropyl-sulfobutyl-β-cyclodextrin (HP-SBE-β-CD) inclusion complex was developed and used as a drug delivery system for DTX (DTX/HP-SBE-β-CD). The objective of the present study was to evaluate and compare the biological properties of DTX/HP-SBE-Β-CD with Taxotere®. The pharmacokinetics, biodistribution, antitumor efficacy in vivo and in vitro, and safety evaluation of DTX/HP-SBE-β-CD were studied. The most significant finding was that it was possible to prepare a Polysorbate-80-free inclusion complex for DTX. Studies based on pharmacokinetics, biodistribution, and antitumor efficacy indicated that DTX/HP-SBE-β-CD had similar pharmacokinetic properties and antitumor efficacy both in vitro and in vivo as Taxotere®. Fortunately, this new drug delivery system attenuated the side effects when used in vivo. As a consequence, DTX/HP-SBE-β-CD may be a promising alternative to Taxotere® for cancer chemotherapy treatment with reduced side effects. The therapeutic potential against a variety of human tumors and low toxicity demonstrated in a stringent study clearly warrant clinical investigation of DTX/HP-SBE-β-CD for possible use against human tumors.Key words: antitumor efficacy, biodistribution, DTX/HP-SBE-β-CD, pharmacokinetics, safety evaluation 相似文献
993.
Enantiomeric amphipathic α-helical antibacterial peptides were synthesized and their biophysical and biological properties under different physiological conditions were studied. In the absence of physiological factors, the l- and d-peptides exhibited similar antimicrobial activities against a broad spectrum of bacteria, even against clinical isolates with resistance to traditional antibiotics. However, in the presence of NaCl, CaCl2 or human serum albumin (HSA) at physiological concentrations, the enantiomers revealed bacterium-species dependent attenuations in antibacterial activity. In the presence of salts the electrostatic interaction between the peptides and the biomembrane was inhibited. Salts, especially CaCl2, weakened the ability of the peptides to permeabilize the outer membrane of Gram-negative bacteria, as determined by a 1-N-phenylnaphthylamine uptake assay. HSA exhibited variable inhibitory effects on the activity of the peptides when incubated with different bacterial strains. The peptides showed different binding association abilities to HSA at different molar ratios, regardless of their chirality, resulting in reduced peptide biological activity. The d-peptide performed better than its l-enantiomer in all conditions tested because of its resistance to proteolysis, and may therefore represent a promising candidate for development as a therapeutic agent. 相似文献
994.
A versatile and highly sensitive probe for Hg(II), Pb(II) and Cd(II) detection individually and totally in water samples 总被引:1,自引:0,他引:1
Zhou Y Tian XL Li YS Zhang YY Yang L Zhang JH Wang XR Lu SY Ren HL Liu ZS 《Biosensors & bioelectronics》2011,30(1):310-314
The detection of heavy metal ions using enzyme-linked immunosorbent assays (ELISA) has been reported by several research groups. However, highly sensitive and selective detection of total heavy metal ions using ELISA is a major technical limitation. Here we describe the development of a versatile and highly sensitive probe combining goat anti-mice IgG, colloidal gold nanoparticles (AuNPs) and horseradish peroxidase (HRP). We demonstrate the utility of this probe using three kinds of heavy metal complete antigens and three monoclonal antibodies (McAbs) in one ELISA system to establish a high-throughput screening protocol. The procedure was successfully applied to analysis of Hg(II), Pb(II) and Cd(II) individually and totally from different water samples. The sensitivities for the detection of Hg(II), Pb(II) and Cd(II) individually and totally are 27.4, 3.9, 15.8 and 18.2 nM, respectively. And all limit of detection (LODs) are lower than 1.2 nM. The recovery results obtained from the developed technique showed a good correlation (R2 = 0.983) with those from ICP-MS. The major advantage of the probe is the versatility and high sensibility. The probe could be potentially used, upon demand, as a sensitive and versatile detector for a broad range of applications. 相似文献
995.
提出顶点及顶点相互作用矢量的概念,并将该矢量用于复杂样本的分子结构表征。采用逐步回归结合统计检测对变量进行筛选后,再用多元线性回归建立了定量结构-色谱保留(QSRR)关系的7变量模型,模型的建模计算值复相关系数(R)为0.990,标准偏差(SD)为1.325;留一法(LOO)交互检验复相关系数(RCV)为0.983,标准偏差(SDCV)为1.696。结果表明该矢量具有较强的分子结构表达能力,模型具有良好的估计能力与稳定性。 相似文献
996.
目的探讨p16和Ki67在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达,研究它们对NSCLC患者预后的影响及其与临床及病理因素之间的关系。方法收集NSCLC术后标本160例及正常肺组织20例(对照组),应用免疫组化法检测NSCLC组织和正常肺组织中p16和Ki67的表达。结果在NSCLC组织和正常肺组织中,p16和Ki67的阳性表达率分别为23.8%、82.5%和90%、5%,差异有统计学意义(P〈0.05)。多因素分析:PTNM分期、淋巴结转移、p16及Ki67的表达是影响NSCLC根治术后患者预后的独立因素(P〈0.05);p16阳性组与阴性组5年生存率分别为55.3%和18.0%,差异有统计学意义(P〈0.05);Ki67阳性组与阴性组5年生存率分别为23.5%和42.9%,差异有统计学意义(P〈0.05),p16和Ki67表达呈负相关(P〈0.05)。结论 p16和Ki67参与了NSCLC的发生发展,p16和Ki67的表达水平与NSCLC的发展及预后有一定的关系。 相似文献
997.
D. Yu. Nazarov A. V. Kucheryavyi K. A. Savvaitova M. A. Gruzdeva K. V. Kuzishchin D. S. Pavlov 《Journal of Ichthyology》2011,51(4):277-290
Phenetic diversity is investigated and the taxonomic status of lampreys (Petromyzontidae) from the Kol basin (Western Kamchatka)
is verified. Typically anadromous lamprey, anadromous lamprey forma praecox, resident lamprey, smolts, and larvae of lamprey
are discovered and described. Their comparative analysis is made by standard morphometric characters. Differences between
the forms by plastic characters depend on size and weight. No significant differences are found by major taxonomic characters
between the forms of anadromous and resident lampreys which would indicate their taxonomic separation. Phenetic types of spawners
are representatives of the population of one complexly structured species represented by life forms realizing different life
history strategies (anadromous and resident), and belong to the species Arctic lamprey Lethenteron camtschaticum (Tilesius, 1811). 相似文献
998.
Yu B Yang M Wong HY Watt RM Song E Zheng BJ Yuen KY Huang JD 《Applied microbiology and biotechnology》2011,91(1):177-188
Live attenuated Salmonella enterica serovar Typhi Ty21a (Ty21a) is an important vaccine strain used in clinical studies for typhoid fever and as a vaccine vector
for the expression of heterologous antigens. To facilitate the use of Ty21a in such studies, it is desirable to develop improved
strategies that enable the stable chromosomal integration and expression of multiple heterologous antigens. The phage λ Red
homologous recombination system has previously been used in various gram-negative bacteria species to mediate the accurate
replacement of regions of chromosomal DNA with PCR-generated ‘targeting cassettes’ that contain flanking regions of shared
homologous DNA sequence. However, the efficiency of λ Red-mediated recombineering in Ty21a is far lower than in Escherichia coli and other Salmonella typhimurium strains. Here, we describe an improved strategy for recombineering-based methods in Ty21a. Our reliable and efficient method
involves the use of linear DNA-targeting cassettes that contain relatively long flanking ‘arms’ of sequence (ca. 1,000 bp)
homologous to the chromosomal target. This enables multiple gene-targeting procedures to be performed on a single Ty21a chromosome
in a straightforward, sequential manner. Using this strategy, we inserted three different influenza antigen expression cassettes
as well as a green fluorescent protein gene reporter into four different loci on the Ty21a chromosome, with high efficiency
and accuracy. Fluorescent microscopy and Western blotting analysis confirmed that strong inducible expression of all four
heterologous genes could be achieved. In summary, we have developed an efficient, robust, and versatile method that may be
used to construct recombinant Ty21a antigen-expressing strains. 相似文献
999.
利用切片方法观察了猞猁Felislynx肝脏的组织结构,应用免疫组织化学方法检测了表皮生长因子(EGF)在肝脏中的表达。结果显示,肝脏外被覆一层结缔组织薄膜,肝小叶不规则且分界不清,肝板、肝血窦及狄氏间隙围绕中央静脉呈放射状排列,肝板由一排肝细胞构成。肝细胞呈圆形或多边形,多为单核,少数具双核,肝细胞间比较松散。肝血窦发达,内可见血细胞。EGF阳性反应主要定位于肝细胞质中,表明EGF可能参与细胞新陈代谢过程的调控。 相似文献
1000.
Xi YD Yu HL Ma WW Ding BJ Ding J Yuan LH Feng JF Xiao R 《Journal of bioenergetics and biomembranes》2011,43(4):399-407
The antioxidative properties of genistein (Gen) have been demonstrated by our previous studies and others, but its potential
mechanism was not very clear. Because of the key role of mitochondria in oxidant production, we wondered if mitochondria were
one of Gen’s neuroprotective targets. In the present study we investigated whether Gen has protective effects on mitochondria
damaged by Aβ25-35. PC12 cells were pre-incubated with or without Gen for 2 h followed by the incubation with 20 μM Aβ25-35
for another 24 h before mitochondrial membrane fluidity (MMF), mitochondrial membrane potential (MMP) , and mitochondrial
redox state were measured. The results showed that Gen alleviated the decrease of MMF induced by Aβ25-35, and maintained the
MMP. Additionally, Gen promoted the mitochondrial antioxidative capability through increasing the GSH/GSSG ratio, GPx activity
and MnSOD protein expression in mitochondria. Moreover, Gen reversed the changes of ChAT mRNA and AChE mRNA expression in
cells induced by Aβ25-35. These results suggested that Gen can protect the mitochondrial membrane and maintain redox state
in mitochondria damaged by Aβ25-35. 相似文献