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951.
A proteomics approach to identifying novel protein targets involved in erinacine A–mediated inhibition of colorectal cancer cells’ aggressiveness 下载免费PDF全文
Ko‐Chao Lee Hsing‐Chun Kuo Chien‐Heng Shen Chien‐Chang Lu Wen‐Shih Huang Meng‐Chiao Hsieh Cheng‐Yi Huang Yi‐Hung Kuo Yung‐Yu Hsieh Chih‐Chuan Teng Li‐Ya Lee Shui‐Yi Tung 《Journal of cellular and molecular medicine》2017,21(3):588-599
Erinacine A, a major active component of a diterpenoid derivative isolated from Hericium erinaceus mycelium, has been demonstrated to exert anticancer effects. Herein, we present an investigation of the molecular mechanism of erinacine A induction associated with cancer cells’ aggressive status and death. A proteomic approach was used to purify and identify the differentially expressed proteins following erinacine A treatment and the mechanism of its action in apoptotic and the targets of erinacine A. Our results demonstrate that erinacine A treatment of HCT‐116 and DLD‐1 cells increased cell cytotoxicity and reactive oxygen species (ROS) production as well as decreased cell proliferation and invasiveness. Ten differentially displayed proteins were determined and validated in vitro and in vivo between the erinacine A‐treated and untreated groups. In addition, erinacine A time‐dependent induction of cell death and inhibitory invasiveness was associated with sustained phosphorylation of the PI3K/mTOR/p70S6K and ROCK1/LIMK2/Cofilin pathways. Furthermore, we demonstrated that erinacine A–induced HCT‐116 and DLD‐1 cells viability and anti‐invasion properties by up‐regulating the activation of PI3K/mTOR/p70S6K and production of ROS. Experiments involving specific inhibitors demonstrated that the differential expression of cofilin‐1 (COFL1) and profilin‐1 (PROF1) during erinacine A treatment could be involved in the mechanisms of HCT‐116 and DLD‐1 cells death and decreased aggressiveness, which occurred via ROCK1/LIMK2/Cofilin expression, with activation of the PI3K/mTOR/p70S6K signalling pathway. These findings elucidate the mechanism of erinacine A inhibiting the aggressive status of cells by activating PI3K/mTOR/p70S6K downstream signalling and the novel protein targets COF1 and PROF1; this could be a good molecular strategy to limit the aggressiveness of CRC cells. 相似文献
952.
Copper increases the ability of 6‐hydroxydopamine to generate oxidative stress and the ability of ascorbate and glutathione to potentiate this effect: potential implications in Parkinson's disease 下载免费PDF全文
Antón Cruces‐Sande Estefanía Méndez‐Álvarez Ramón Soto‐Otero 《Journal of neurochemistry》2017,141(5):738-749
953.
954.
Angelika Bröer Sarojini Balkrishna Gabor Kottra Sarah Davis Aaron Oakley 《Molecular membrane biology》2013,30(5-7):333-346
The system IMINO transporter plays an essential role in the transport of proline and hydroxyproline in the intestine and kidney. Its molecular correlate has been identified and named SIT1 or IMINO (SLC6A20). Initial characterization of the transporter showed it to be Na+ and Cl?-dependent, but the stoichiometry remained unresolved. Using homology modeling along the structure of the bacterial leucine transporter LeuT, we identified two highly conserved Na+-binding sites and a putative Cl?-binding site. Mutation of all residues in the two proposed Na+-binding sites revealed that most of them were essential for uptake and completely inactivated the transporter. However, mutants A22V (Na+-binding site 1) and mutants S20A, S20G, S20G/G405S (Na+-binding site 2) were partially active and characterized further. Flux studies suggested that mutations of Na+-binding site 1 caused a decrease of the Na+-K0.5, whereas mutations of site 2 increased the K0.5. Mutation of Na+-binding site 1 also changed the ion selectivity of the IMINO transporter. IMINO actively translocates 36Cl? demonstrating that the proposed chloride binding site is used in the transporter. Accumulation experiments and flux measurements at different holding potentials showed that the transporter can work as a 2Na+/1Cl?-proline cotransporter. The proposed homology model allows to study mutations in IMINO associated with iminoglycinuria. 相似文献
955.
Matthias Hoch Estelle Hirzel Peter Lindinger Philippe Linscheid Ivan Martin 《Journal of receptor and signal transduction research》2013,33(5):485-504
The melanocortin (MC) receptor type-1 (MC1-R) is the only one of the five MC receptor subtypes expressed in human adipose tissue explants, human mesenchymal stem cells (MSCs), and MSC-derived adipocytes. Following our recent expression studies (Obesity 2007, 15, 40–49), we now investigated the functional role of MC1-R in these tissues and cells to deduce the coupling state of MC1-R to intracellular output signals in human fat cells and tissue. Expression of MC1-R by undifferentiated and differentiated MSCs was quantified by real-time TaqMan PCR. Intracellular output signals (cAMP, lipolysis, secretion of IL-6, IL-10, and TNF-α), as well as effects on the metabolic rate and proliferation of human MSCs were analyzed by standard assays, exposing undifferentiated and differentiated MSCs and, in part, human adipose tissue explants to the potent MC1-R agonist, [Nle4, D-Phe7]-α -MSH (NDP-MSH). This agonist induced a weak cAMP signal in MSC-derived adipocytes. However, it did not affect lipolysis in these cells or in adipose tissue explants, nor did it modulate cytokine release and mRNA expression of IL-6, IL-8, and TNF-α upon LPS stimulation. In undifferentiated MSCs, NDP-MSH did not alter the metabolic rate, but it showed a significant antiproliferative effect. Therefore, it appears that MC1-R–effector coupling in (differentiated) human adipocytes is too weak to induce a regulatory effect on lipolysis or inflammation; by contrast, MC1-R stimulation in undifferentiated MSCs induces an inhibitory signal on cell proliferation. 相似文献
956.
Erik C. Van Os Jeffrey A. McKinney Bradley J. Zins Dennis C. Mays Zachary H. Schriver William J. Sandborn James J. Lipsky 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1996,679(1-2)
A specific, sensitive, single-step solid-phase extraction and reversed-phase high-performance liquid chromatographic method for the simultaneous determination of plasma 6-mercaptopurine and azathioprine concentrations is reported. Following solid-phase extraction, analytes are separated on a C18 column with mobile phase consisting of 0.8% acetonitrile in 1 mM triethylamine, pH 3.2, run on a gradient system. Quantitation limits were 5 ng/ml and 2 ng/ml for azathioprine and 6-mercaptopurine, respectively. Peak heights correlated linearly to known extracted standards for 6-mercaptopurine and azathioprine (r = 0.999) over a range of 2–200 ng/ml. No chromatographic interferences were detected. 相似文献
957.
This experiment examined dopamine D2 receptor and its transporter (DAT) density in mice fed a high-fat or low-fat diet for
twenty days as well as fed twenty days of high-fat diet then changed to low-fat diet for one and seven days. Quantitative
autoradiography revealed that twenty days of high-fat diet consumption significantly increased D2 receptor and decreased DAT
density in the dorsal and ventral parts of the caudal caudate putamen (D2: 32% and 35% respectively, DAT: 33.3% and 28.8%
respectively) compared with low-fat diet. High-fat feeding also increased D2 binding in the nucleus accumbens shell (36%).
D2 receptor and DAT density remained unchanged following reversal of the diets from high-fat to low-fat diet. The high-fat
diet induced increase of D2 receptor and decrease of DAT binding may have occurred due to defensive control over dopaminergic
activity in response to a positive energy balance. 相似文献
958.
959.
Katoh S 《Photosynthesis research》2003,76(1-3):255-261
A review is presented of the early history of investigations into the function of the blue copper-protein plastocyanin in
photosynthesis. The controversy or confusion that arose as to the function of plastoycanin in conjunction with cytochrome
f and cytochrome c
6 is discussed and investigations contributing to the establishment of the role of plastocyanin as the mobile electron carrier
between the Photosystem I reaction center complex and the cytochrome b
6/f complex are described.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
960.
摘要 目的:探讨涎液化糖链抗原(KL-6)、基质金属蛋白酶-7(MMP-7)和透明质酸(HA)联合诊断结缔组织病合并间质性肺疾病(ILD)的价值。方法:选取2017年12月至2019年12月本院收治的69例结缔组织病合并ILD患者作为本文研究对象(合并ILD组),以单纯结缔组织病患者67例,同期体检的60例健康受试者分别作为单纯结缔组织病组和对照组。比较三组受试者血清KL-6、MMP-7和HA,Logistic回归分析确定结缔组织病发生ILD的独立影响因素,通过受试者工作特征(ROC)曲线分析诊断效能。结果:三组血清KL-6、MMP-7和HA水平有差异(P<0.05),合并ILD组患者血清KL-6、MMP-7和HA水平明显高于单纯结缔组织病组和对照组(P<0.05),单纯结缔组织病组患者血清KL-6、MMP-7和HA水平明显高于对照组(P<0.05)。Logistic回归分析结果表明,血清KL-6、MMP-7、HA等三指标及粉尘接触史均是结缔组织病发生ILD的显著影响因素(P<0.05)。 ROC分析显示: 血清KL-6、MMP-7和HA等三指标诊断结缔组织病发生ILD的AUC(0.95CI)分别为0.715(0.439~0.988)、0.702(0.440~0.959)、0.711(0.500~0.919),三指标联合应用的AUC(0.95CI)为0.811(0.705~0.913),诊断效能较高。结论:结缔组织病合并ILD患者血清KL-6、MMP-7及HA升高,联合应用诊断可提高对ILD的诊断效能,为早期诊断ILD提供一定的参考。 相似文献