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61.
Reviews the book, Drugs and behavior: An introduction to behavioral pharmacology by William A. McKim (1986). This book effectively describes in 14 chapters the diverse aspects of behavioural pharmacology. The structure of the chapters ensures that a continuity of basic principles in behavioural pharmacology will emerge, and the reader will be able to understand the behavioural consequences of drugs with respect to their physiology and pharmacology in each chapter. This book covers the material well, and in my opinion its greatest strength is its readability. The author produced a book that will not only give undergraduate and graduate students a solid foundation in behavioural pharmacology, but will also provide an enjoyable reading experience. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
62.
Exploring the Effects of Glycosylation and Etherification of the Side Chains of the Anticancer Drug Mitoxantrone 下载免费PDF全文
Pazit Shaul Kfir B. Steinbuch Eran Blacher Prof. Reuven Stein Dr. Micha Fridman 《ChemMedChem》2015,10(9):1528-1538
Herein we report the synthesis and biological evaluation of symmetric and asymmetric analogues of the DNA intercalating drug mitoxantrone (MTX) in which the side chains of the parent drug were modified through glycosylation or methyl etherification. Several analogues with glycosylated side chains exhibited higher DNA affinity than the parent MTX. The most potent in vitro cytotoxicity was observed for MTX analogue 8 (1,4‐dimethoxy‐5,8‐bis[2‐(2‐methoxyethylamino)ethylamino]anthracene‐9,10‐dione) with methoxy ether containing side chains. Treatment of melanoma‐bearing mice with MTX or analogue 8 decreased the intraperitoneal tumor burden relative to untreated mice; the effect of 8 was less pronounced than that of MTX. In vitro metabolism assays of MTX with rabbit liver S9 fraction gave rise to several metabolites; almost no metabolites were detected for MTX analogue 8 . The results presented indicate that derivatization of the MTX side chain primary hydroxy groups may result in a significant improvement in DNA affinity and lower susceptibility to the formation of potentially toxic metabolites. 相似文献
63.
Peptide Bioconjugates of Electron‐Poor Metallocenes: Synthesis,Characterization, and Anti‐Proliferative Activity 下载免费PDF全文
Marcus Maschke Jens Grohmann Claudia Nierhaus Dr. Max Lieb Prof. Dr. Nils Metzler‐Nolte 《Chembiochem : a European journal of chemical biology》2015,16(9):1333-1342
We report the synthesis of metallocene compounds Cp2M with two different electron‐withdrawing substituents on both cyclopentadienyl rings (hexafluoroacetone (HFA) and chlorobenzoyl ( 1 – 5 ); HFA and COOH ( 6 and 7 ), M=Fe or Ru). The COOH‐containing derivatives were used to synthesize peptide bioconjugates with enkephalin ( 8 and 9 ) and neurotensin ( 10 and 11 ) as well as fluorescein‐labeled neurotensin ( 12 ). All the molecules were fully characterized, including X‐ray structures for 6 and 7 . The physicochemical properties (lipophilicity and electrochemistry) and cytotoxicity on MCF‐7, HT‐29, and PT‐45 cancer cells were evaluated for selected compounds. Electrochemical investigation by cyclic voltammetry revealed that all bis‐substituted metallocenes are up to 300 mV harder to oxidize compared to the monosubstituted 2‐ferrocenylhexafluoropropan‐2‐ol (FcHFA: Δ${E{{{\rm f}\hfill \atop 0\hfill}}}$ =214 mV; disubstituted derivatives: up to Δ${E{{{\rm f}\hfill \atop 0\hfill}}}$ =512 mV; both vs. FcH0/+). For the bis‐substituted compounds, log P determinations by RP‐HPLC showed increased lipophilicity in comparison to the monosubstituted FcHFA and RcHFA. Cellular uptake was investigated by fluorescence microcopy, and this revealed endosomal entrapment for 12 . 相似文献
64.
Priv. Doz. Dr. Felix Zelder Marjorie Sonnay Lucas Prieto 《Chembiochem : a European journal of chemical biology》2015,16(9):1264-1278
Antivitamins represent a broad class of compounds that counteract the essential effects of vitamins. The symptoms triggered by such antinutritional factors resemble those of vitamin deficiencies, but can be successfully reversed by treating patients with the intact vitamin. Despite being undesirable for healthy organisms, the toxicities of these compounds present considerable interest for biological and medicinal purposes. Indeed, antivitamins played fundamental roles in the development of pioneering antibiotic and antiproliferative drugs, such as prontosil and aminopterin. Their development and optimisation were made possible by the study, throughout the 20th century, of the vitamins' and antivitamins' functions in metabolic processes. However, even with this thorough knowledge, commercialised antivitamin‐based drugs are still nowadays limited to antagonists of vitamins B9 and K. The antivitamin field thus still needs to be explored more intensely, in view of the outstanding therapeutic success exhibited by several antivitamin‐based medicines. Here we summarise historical achievements and discuss critically recent developments, opportunities and potential limitations of the antivitamin approach, with a special focus on antivitamins K, B9 and B12. 相似文献
65.
66.
Krizkova S Fabrik I Huska D Adam V Babula P Hrabeta J Eckschlager T Pochop P Darsova D Kukacka J Prusa R Trnkova L Kizek R 《International journal of molecular sciences》2010,11(12):4826-4842
The drugs based on platinum metals represent one of the oldest, but also one of the most effective groups of chemotherapeutic agents. Thanks to many clinical studies it is known that resistance of tumor cells to drugs is a frequent cause of chemotherapy failure. With regard to platinum based drugs, multidrug resistance can also be connected with increased expression of low-molecular weight protein metallothionein (MT). This study aimed at investigating the interactions of MT with cisplatin or carboplatin, using the adsorptive transfer technique coupled with differential pulse voltammetry Brdicka reaction (AdTS DPV Brdicka reaction), and a comparison of in vitro results with results obtained in vivo. The results obtained from the in vitro study show a strong affinity between platinum based drugs and MT. Further, we analyzed extracts of neuroblastoma cell lines treated with cisplatin or carboplatin. It is clear that neuroblastoma UKF-NB-4 cisplatin-resistant and cisplatin-sensitive cell lines unlikely respond to the presence of the platinum-based cytostatics cisplatin and carboplatin. Finally, we determined the level of MT in samples from rabbits treated with carboplatin and patients with retinoblastoma treated with the same drug. 相似文献
67.
综述了化学法和化学—生物结合法制备蛋白质药物的一些实例,重点介绍了(His)6-tag辅助法和蛋白质内含子介导法。 相似文献
68.
建立QuEChERS结合超高效液相色谱-串联质谱(ultra-high performance liquid chromatography-tandem mass spectrometry,UPLC-MS/MS)法快速测定猪肉、牛肉和羊肉中8 种抗真菌药物(氟康唑、酮康唑、萘替芬、联苯苄唑、克霉唑、益康唑、灰黄霉素、咪康唑)残留量的分析方法。利用加标样品对提取溶剂、提取时间、吸附剂种类、吸附剂用量及加盐量等参数进行优化,在最佳提取和检测条件下,采用正离子多反应监测模式分析和外标法定量,8 种抗真菌药物在7 min内完成测定,在0.05~10.00 ng/mL质量浓度范围内线性关系良好(r>0.998),检出限为0.1 μg/kg,定量限为0.3 μg/kg。在畜肉样品中添加8 种抗真菌药物具有良好的重复性和稳定性,准确度在15%以内,日内(n=6)平均回收率为85.7%~113.6%,日间(n=3)平均回收率为87.6%~107.9%,变异系数为1.2%~14.8%。QuEChERS结合UPLC-MS/MS处理过程简单、快速、高效、准确,可用于畜肉中8 种抗真菌药物残留量的快速定性和定量分析。 相似文献
69.
摘要: 目的 建立一种无需标准品即可快速检测保健品中136种非法添加降血压药物的超高效液相色谱-四极杆/静电场轨道阱高分辨质谱分析方法。方法 样品经甲醇溶液适当稀释,超声处理后,经 Waters Acquity BEH C18色谱柱(100 mm×2.1 mm, 1.7 μm)分离,以0.1% (V:V)甲酸水溶液-乙腈作为流动相, 进行梯度洗脱。加热电喷雾离子源正负离子同时采集,一级母离子全扫描和数据依赖的二级子离子扫描模式检测,将采集的样品质谱信息与自建立的136种非法添加降血压药物质谱信息库通过分子离子精准质量数比对、同位素分布比对进行初筛,初筛出的阳性化合物通过二级碎片离子解析进行进一步确证。结果 该方法能够在没有标准品的情况下,在20 min内对保健食品中136种非法添加降压药物同时进行精准筛查,14种降压药物的添加回收实验表明实际样品的检出限在2.0~3.0 ?g/kg,采用本方法对市售实际样品进行检验, 1款声称具有降血脂的保健食品中有坎地沙坦酯检出。结论 该方法通量高、速度快、成本低,可用于保健食品中非法添加降血压药物的快速筛查。 相似文献
70.
建立了超高效液相色谱-四极杆-飞行时间质谱(UPLC-Q-TOF/MS)快速筛查畜禽类产品中50种违禁药物残留的检测方法。畜禽类产品经β-葡萄糖醛酸酶/芳基硫酸酯酶酶解,依次用乙酸乙酯-叔丁基甲醚提取后,利用HLB净化,采用UPLC-Q-TOF/MS电喷雾正离子模式检测。通过建立在线谱库检索的方法实现50种违禁药物的快速筛选和准确定性,再结合同位素内标法实现准确定量。目标物质量浓度在2~200 μg/L范围内线性关系良好,相关系数均大于0.99,检出限为0.1~0.5 μg/kg,定量限为0.3~1.5 μg/kg,三个不同浓度的加标回收率在81.74%~114.22%之间,相对标准偏差为1.41%~8.91%。研究建立的筛查数据库在无需标准品的情况下实现了50种违禁药物的快速筛查、定性确证和定量分析。该方法适用于畜禽类产品中低浓度的违禁药物残留量的快速筛查和准确定量。 相似文献