收费全文 | 10623篇 |
免费 | 960篇 |
国内免费 | 557篇 |
工业技术 | 12140篇 |
2024年 | 14篇 |
2023年 | 161篇 |
2022年 | 345篇 |
2021年 | 535篇 |
2020年 | 397篇 |
2019年 | 310篇 |
2018年 | 327篇 |
2017年 | 361篇 |
2016年 | 310篇 |
2015年 | 430篇 |
2014年 | 491篇 |
2013年 | 582篇 |
2012年 | 675篇 |
2011年 | 675篇 |
2010年 | 657篇 |
2009年 | 667篇 |
2008年 | 623篇 |
2007年 | 598篇 |
2006年 | 633篇 |
2005年 | 493篇 |
2004年 | 324篇 |
2003年 | 347篇 |
2002年 | 286篇 |
2001年 | 222篇 |
2000年 | 250篇 |
1999年 | 247篇 |
1998年 | 180篇 |
1997年 | 175篇 |
1996年 | 145篇 |
1995年 | 125篇 |
1994年 | 109篇 |
1993年 | 100篇 |
1992年 | 86篇 |
1991年 | 63篇 |
1990年 | 49篇 |
1989年 | 38篇 |
1988年 | 36篇 |
1987年 | 19篇 |
1986年 | 13篇 |
1985年 | 12篇 |
1984年 | 6篇 |
1983年 | 7篇 |
1982年 | 6篇 |
1981年 | 3篇 |
1980年 | 6篇 |
1979年 | 1篇 |
1951年 | 1篇 |
Construction of multifunctional stimuli-responsive nanotherapeutics enabling improved intratumoral penetration of therapeutics and reversal of multiple-drug resistance (MDR) is potent to achieve effective cancer treatment. Herein, we report a general method to synthesize pH-dissociable calcium carbonate (CaCO3) hollow nanoparticles with amorphous CaCO3 as the template, gallic acid (GA) as the organic ligand, and ferrous ions as the metallic center via a one-pot coordination reaction. The obtained GA–Fe@CaCO3 exhibits high loading efficiencies to both oxidized cisplatin prodrug and doxorubicin, yielding drug loaded GA–Fe@CaCO3 nanotherapeutics featured in pH-responsive size shrinkage, drug release, and Fenton catalytic activity. Compared to nonresponsive GA–Fe@silica nanoparticles prepared with silica nanoparticles as the template, such GA–Fe@CaCO3 confers significantly improved intratumoral penetration capacity. Moreover, both types of drug-loaded GA–Fe@CaCO3 nanotherapeutics exhibit synergistic therapeutic efficacies to corresponding MDR cancer cells because of the GA–Fe mediated intracellular oxidative stress amplification that could reduce the efflux of engulfed drugs by impairing the mitochondrial-mediated production of adenosine triphosphate (ATP). As a result, it is found that the doxorubicin loaded GA–Fe@CaCO3 exhibits superior therapeutic effect towards doxorubicin-resistant 4T1 breast tumors via combined chemodynamic and chemo-therapies. This work highlights the preparation of pH-dissociable CaCO3-based nanotherapeutics to enable effective tumor penetration for enhanced treatment of drug-resistant tumors.
相似文献Vulnerable atherosclerotic plaques are responsible for most cardiovascular diseases (CVDs). Folate receptor (FR) positive activated macrophages were thought to be a prominent component in the development of vulnerable plaque. The objective of this study is to develop folate conjugated two-dimensional (2D) Pd@Au nanomaterials (Pd@Au-PEG-FA) for targeted multimodal imaging of the FRs in advanced atherosclerotic plaques. Pharmacokinetic and imaging studies (single photon emission computed tomography (SPECT), computed tomography (CT) and photoacoustic (PA) imaging) were performed to confirm the prolonged blood half-life and enrichment of radioactivity in atherosclerotic plaques. Strong signals were detected in vivo with SPECT, CT and PA imaging in heavy atherosclerotic plaques, which were significantly higher than those of the normal aortas after injection of Pd@Au-PEG-FA. Blocking studies with preinjection of excess FA could effectively reduce the targeting ability of Pd@Au-PEG-FA in atherosclerotic plaques, further demonstrating the specific binding of Pd@Au-PEG-FA for plaque lesions. Histopathological characterization revealed that the signal of probe was in accordance with the high-risk plaques. In summary, the Pd@Au-PEG-FA has favorable pharmacokinetic properties and provides a valuable approach for detecting high-risk plaques in the presence of FRs in atherosclerotic plaques.
相似文献Large scale synthesis of high-efficiency bifunctional electrocatalyst based on cost-effective and earth-abundant transition metal for overall water splitting in the alkaline environment is indispensable for renewable energy conversion. In this regard, meticulous design of active sites and probing their catalytic mechanism on both cathode and anode with different reaction environment at molecular-scale are vitally necessary. Herein, a coordination environment inheriting strategy is presented for designing low-coordination Ni2+ octahedra (L-Ni-8) atomic interface at a high concentration (4.6 at.%). Advanced spectroscopic techniques and theoretical calculations reveal that the self-matching electron delocalization and localization state at L-Ni-8 atomic interface enable an ideal reaction environment at both cathode and anode. To improve the efficiency of using the self-modification reaction environment at L-Ni-8, all of the structural features, including high atom economy, mass transfer, and electron transfer, are integrated together from atomic-scale to macro-scale. At high current density of 500 mA/cm2, the samples synthesized at gram-scale can deliver low hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) overpotentials of 262 and 348 mV, respectively.
相似文献