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排序方式: 共有7493条查询结果,搜索用时 17 毫秒
1.
Lili Chen Nanami Fujisawa Masato Takanohashi Mazaya Najmina Koichiro Uto Mitsuhiro Ebara 《International journal of molecular sciences》2021,22(5)
This study demonstrates the rational fabrication of a magnetic composite nanofiber mesh that can achieve mutual synergy of hyperthermia, chemotherapy, and thermo-molecularly targeted therapy for highly potent therapeutic effects. The nanofiber is composed of biodegradable poly(ε-caprolactone) with doxorubicin, magnetic nanoparticles, and 17-allylamino-17-demethoxygeldanamycin. The nanofiber exhibits distinct hyperthermia, owing to the presence of magnetic nanoparticles upon exposure of the mesh to an alternating magnetic field, which causes heat-induced cell killing as well as enhanced chemotherapeutic efficiency of doxorubicin. The effectiveness of hyperthermia is further enhanced through the inhibition of heat shock protein activity after hyperthermia by releasing the inhibitor 17-allylamino-17-demethoxygeldanamycin. These findings represent a smart nanofiber system for potent cancer therapy and may provide a new approach for the development of localized medication delivery. 相似文献
2.
海域试开采区域含水合物沉积物的粒度分析结果表明水合物沉积物骨架由粗、细颗粒混合构成,通过开展多组低温、高压三轴排水剪切试验研究细颗粒含量和密度对含甲烷水合物沉积物和无水合物沉积物的强度和变形特性的影响。试验结果表明,含水合物沉积物抗剪强度及剪胀性都随细粒含量提高而显著增强。这是由于细颗粒含量增加改变了颗粒间水合物的样貌和分布特征,形成了由水合物包裹着粗颗粒-细颗粒的团簇状集合体。然而,细颗粒含量对无水合物沉积物的强度和变形特性的影响却表现出相反趋势。另外,含水合物沉积物的剪胀关系可以使用修正剑桥模型中的剪胀关系式进行描述。结果表明,剪胀关系的拟合曲线依赖于水合物饱和度的大小。通过对比研究发现,天然水合物和实验室合成水合物试样在较高饱和度时的峰值摩擦角大小及其伴随水合物饱和度的增长趋势存在差异,这种差异主要来源于水合物在沉积物骨架颗粒孔隙中不同的赋存模式及分布特征。 相似文献
3.
Dr. Daniel Feder Dr. Siti H. Mohd-Pahmi Dr. Waleed M. Hussein Prof. Luke W. Guddat Prof. Ross P. McGeary Prof. Gerhard Schenk 《ChemMedChem》2021,16(21):3342-3359
Metallohydrolases form a large group of enzymes that have fundamental importance in a broad range of biological functions. Among them, the purple acid phosphatases (PAPs) have gained attention due to their crucial role in the acquisition and use of phosphate by plants and also as a promising target for novel treatments of bone-related disorders and cancer. To date, no crystal structure of a mammalian PAP with drug-like molecules bound near the active site is available. Herein, we used a fragment-based design approach using structures of a mammalian PAP in complex with the MaybridgeTM fragment CC063346, the amino acid L-glutamine and the buffer molecule HEPES, as well as various solvent molecules to guide the design of highly potent and efficient mammalian PAP inhibitors. These inhibitors have improved aqueous solubility when compared to the clinically most promising PAP inhibitors available to date. Furthermore, drug-like fragments bound in newly discovered binding sites mapped out additional scaffolds for further inhibitor discovery, as well as scaffolds for the design of inhibitors with novel modes of action. 相似文献
4.
天然气水合物储层泥质细粉砂挡砂介质堵塞规律与微观挡砂机制 总被引:1,自引:0,他引:1
中国南海海域部分天然气水合物储层中地层砂为高泥质含量细粉砂,开采防控砂难度较大。针对高泥质细粉砂挡砂机制问题,使用粒度中值为10.13 μm的泥质细粉砂样品,模拟单向气液携砂流动条件,使用绕丝筛板、金属烧结网、金属纤维、预充填陶粒4类挡砂介质在20~80 μm挡砂精度下进行挡砂模拟实验,采用显微成像系统观察挡砂介质内部及表面砂粒沉积与堵塞动态,分析介质流通性能和挡砂性能变化,总结堵塞规律、微观挡砂机制与形态及其控制因素。研究结果表明,不同类型和精度的挡砂介质对泥质细粉砂的堵塞总体呈现堵塞开始、堵塞加剧和堵塞平衡3个阶段。随着驱替进行,挡砂介质渗透率逐渐降低,幅度会高达90%以上;同时过砂速度减缓,最终过砂率为5%~10%。根据堵塞规律和微观图像分析,提出了粗组分分选桥架、局部砂团适度挡砂、整体砂桥阻挡等挡砂介质对泥质细粉砂的3种微观挡砂机制。以粗组分分选桥架挡砂机制为主的挡砂工况下,挡砂介质堵塞渗透率较高,但过砂率超过15%,挡砂效果较差;以整体砂桥挡砂机制为主时,过砂率在10%以下,挡砂性能较好,但各类挡砂介质的堵塞渗透率不足1 D,流通性能较差。局部砂团适度挡砂机制为主时介质挡砂性能及流通性能介于两者之间。挡砂介质对天然气水合物储层泥质细粉砂的微观挡砂机制和形态受挡砂介质类型、精度、地层砂特征以及流动条件等因素控制,其规律对于水合物泥质细粉砂防控砂优化有指导意义。 相似文献
5.
Marta Baranowska-Kuczko Hanna Kozowska Monika Kloza Ewa Harasim-Symbor Micha Biernacki Irena Kasacka Barbara Malinowska 《International journal of molecular sciences》2021,22(9)
Our study aimed to examine the effects of hypertension and the chronic administration of the fatty acid amide hydrolase (FAAH) inhibitor URB597 on vascular function and the endocannabinoid system in spontaneously hypertensive rats (SHR). Functional studies were performed on small mesenteric G3 arteries (sMA) and aortas isolated from SHR and normotensive Wistar Kyoto rats (WKY) treated with URB597 (1 mg/kg; twice daily for 14 days). In the aortas and sMA of SHR, endocannabinoid levels and cannabinoid CB1 receptor (CB1R) expression were elevated. The CB1R antagonist AM251 diminished the methanandamide-evoked relaxation only in the sMA of SHR and enhanced the vasoconstriction induced by phenylephrine and the thromboxane analog U46619 in sMA in SHR and WKY. In the sMA of SHR, URB597 elevated anandamide levels, improved the endothelium-dependent vasorelaxation to acetylcholine, and in the presence of AM251 reduced the vasoconstriction to phenylephrine and enhanced the vasodilatation to methanandamide, and tended to reduce hypertrophy. In the aortas, URB597 elevated endocannabinoid levels improved the endothelium-dependent vasorelaxation to acetylcholine and decreased CB1R expression. Our study showed that hypertension and chronic administration of URB597 caused local, resistance artery-specific beneficial alterations in the vascular endocannabinoid system, which may bring further advantages for therapeutic application of pharmacological inhibition of FAAH. 相似文献
6.
7.
Keshun Liu 《Journal of the American Oil Chemists' Society》2019,96(6):635-645
For measuring trypsin inhibitor (TI) activities in soybean products, the current standard method, approved and reapproved by American Oil Chemists Society (Method Ba 12-75) and American Association of Cereal Chemists International (Method 22-40.01), features mixing trypsin with a series of inhibitor levels and then adding a substrate to start the colorimetric reaction. Yet, previous studies have shown flaws with the method, particularly with using several inhibitor levels and the sequence of adding the substrate last. The present study showed that with varying levels of dilution and volumes of a dilute sample extract, the pH of the premix (the mixture of a dilute sample extract and trypsin solution) ranged 3.30–3.60 for raw soy flour, and 3.20–6.70 for toasted soy. Within these premix pH ranges, the standard method of adding substrate last would give TI values equal to or less than those measured by the same method except for adding the enzyme last. The standard method was subsequently improved by using a single sample extract level and the enzyme-last sequence. Other modifications included making stock solutions for reagents, adding Ca2+ to the trypsin solution, diluting sample extracts to a level that causes 30–70% of inhibition, and running both reference and sample blanks for better controls. Alternatively, the full volume assay (10 mL total, as in the standard method) was further modified by using half the volume of each reagent with the same concentration. Compared to the standard method, the improved methods gave more consistent results when assaying 11 selected soy products. The half volume (5 mL) and full volume methods gave the same results, but the former could increase assay sensitivity and reduce amounts of reagents used. 相似文献
8.
布鲁顿式酪氨酸激酶(Btk)和两面神激酶3(JAK3)均是自身免疫性疾病和血液系统恶性肿瘤的潜力靶标。以4-氯吡咯并嘧啶为原料,经7步反应合成了一系列7H-吡咯并[2,3-d]嘧啶-4-胺衍生物,其结构经1HNMR、13CNMR和MS(ESI)分析证实。体外依次考察了所得化合物分别对Btk和JAK3激酶的活性、以及对部分B淋巴细胞瘤细胞系的抗增殖活性。结果表明,四氢吡咯烷基取代的衍生物NB1~4对Btk(IC50<3 nmol/L)和JAK3(IC50<165 nmol/L)均能有效抑制,其余化合物只对Btk显示抑制效果;而且NB2和NB4对所测试的多种B细胞淋巴瘤细胞系的抗增殖活性均优于阳性对照泛激酶抑制剂依鲁替尼及Btk单靶点抑制剂。其中,对Jeko-1细胞的抑制能力最佳(IC50<3μmol/L),其次是OCI-LYI(IC50<4μmol/L)、SUDHL-6(IC50<6μmol/L)和HBL-1*(IC50<6.5μmol/L),最差为SUDHL-4细胞(IC50<11μmol/L)。这些发现可为开发B细胞淋巴瘤的多靶点药物提供新的思路。 相似文献
9.
10.
水合物的存在会显著影响能源土的刚度、峰值强度与剪胀性。针对已有能源土模型的不足,结合边界面模型的建模思想,构建一个新的能源土边界面模型,模型参数较少,能够恰当反映能源土的应力-应变关系。计算能源土变形问题的核心在于正确积分塑性本构方程,应用完全隐式回退Euler算法,建立模型应力及塑性内变量的更新公式,并给出显式的一致性切线模量表达式。基于ABAQUS软件提供的二次开发接口,编写模型的用户材料子程序,应用已有试验数据验证程序正确性。最后应用开发的子程序对能源土的平面应变试验进行模拟,分析水合物饱和度对剪切带倾角与孔隙比的影响。 相似文献