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1.
《药学学报(英文版)》2020,10(5):895-902
Seven indole alkaloid glycosides containing a 1′-(4″-hydroxy-3″,5″-dimethoxyphenyl)ethyl unit (1–7) were isolated from an aqueous extract of Isatis indigotica leaves (da qing ye). Their structures were determined by spectroscopic data analysis combined with enzymatic hydrolysis as well as comparison of their experimental CD (circular dichroism) and calculated ECD (electrostatic circular dichroism) spectra. Based on analysis of and/or Cotton effect (CE) data of 1–7, two simple roles to assign location and/or configuration of β-glycopyranosyloxy and 1′-(phenyl)ethyl units in the indole alkaloid glycosides are proposed. Stereoselectivity in plausible biosynthetic pathways of 1–7 is discussed. Compounds 3 and 4 and their mixture in a 3:2 ratio showed activity against KCNQ2 in CHO cells. The mixture of 5 and 6 (3:2) exhibited antiviral activity against influenza virus H1N1 PR8 with IC50 64.7 μmol/L (ribavirin, IC50 54.3 μmol/L), however, the individual 5 or 6 was inactive. Preliminary structure–activity relationships were observed. 相似文献
2.
Shingo Ito Yu Fujino Seiryo Ogata Mio Hirayama-Kurogi Sumio Ohtsuki 《Journal of pharmaceutical sciences》2018,107(12):3163-3170
The SLC22A18 gene, which encodes an orphan transporter, is located at the 11p15.5 imprinted region, an important tumor suppressor gene region. However, the role of SLC22A18 in tumor suppression remains unclear. Here, we investigated the involvement of SLC22A18 in cell growth, invasion, and drug resistance of MCF7 human breast cancer cell line. Western blot analysis indicated that SLC22A18 is predominantly expressed at intracellular organelle membranes. Quantitative proteomics showed that knockdown of SLC22A18 significantly altered the expression of 578 (31.0%) of 1867 proteins identified, including proteins related to malignancy and poor prognosis of breast cancer. SLC22A18 knockdown (1) increased MCF7 cell growth concomitantly with a >7-fold increase of annexin A8 (involved in cell growth and migration; a predictor of poor prognosis), (2) induced spherical morphology of MCF7 cells concomitantly with a nearly 3-fold increase of CD44 (involved in regulation of malignant phenotypes), and (3) increased chemosensitivity to vinca alkaloids concomitantly with a >80% reduction of doublecortin-like kinase 1 (involved in regulation of microtubule polymerization). Our results suggest that SLC22A18 may act as a tumor suppressor by regulating the expression levels of cell growth–related proteins, and vinca alkaloids might show therapeutic efficacy against low-SLC22A18–expressing breast cancer. 相似文献
3.
多指标综合评分法优化痛风巴布剂的醇提工艺 总被引:1,自引:1,他引:0
目的 优选痛风巴布剂的最佳提取工艺。方法 以青藤碱、总生物碱的含量和干浸膏得率为评价指标,采用正交设计试验,考察乙醇浓度、乙醇用量、提取时间和提取次数对提取结果的影响,确定痛风巴布剂处方药材的最佳提取工艺。结果 痛风巴布剂的最佳提取工艺为65%乙醇,提取3次,每次6倍量溶剂,提取总时间为1.5 h,在该工艺条件下得到的青藤碱含量、总生物碱含量和干浸膏得率分别为2.79 mg·g-1、1.22%和13.06%。结论 优选的醇提工艺稳定、可行。 相似文献
4.
目的:建立坤泰胶囊中化学成分的高效液相色谱-电喷雾质谱联用技术(HPLC-ESI-MS/MS)并对其化学成分进行初步鉴定。方法:采用LC-ESI-MS/MS对坤泰胶囊进行成分分析与鉴定,选用C_(18)色谱柱(4.6 mm×150 mm,5μm),以乙腈-0.1%甲酸水溶液为流动相梯度洗脱,流速1.0 mL·min~(-1),柱温30℃。质谱使用电喷雾(ESI)离子源,正离子模式采集数据。质量扫描范围为m/z 50~1 500。对各色谱峰质谱图进行分析,根据准分子离子峰判断相对分子质量,进一步根据各主要碎片离子、紫外光谱、保留时间等信息,与文献数据进行比较推测化合物的结构。结果:从坤泰胶囊中鉴定了21个化合物,主要为黄酮类化合物和生物碱类化合物,并对化合物的药材来源进行了归属。其中,主要有来自黄芩的黄芩苷、汉黄芩苷、黄芩素、汉黄芩素等,来自黄连的巴马汀、小檗碱、黄连碱、药根碱、非洲防己碱、木兰花碱等,来自白芍的芍药苷等。结论:采用LC-ESIMS/MS能够对坤泰胶囊中主要成分进行快速分析与鉴定,为坤泰胶囊进一步开展指纹图谱、质量控制、药物代谢研究和谱效关系研究奠定了基础。 相似文献
5.
6.
含吡咯里西啶生物碱中成药潜在风险评估 总被引:3,自引:2,他引:1
吡咯里西啶生物碱(pyrrolizidine alkaloids,PAs)是一种双环吡咯啶生物碱,因多数具有肝毒性,又称肝毒性吡咯里西啶生物碱(hepatotoxic PAs)。PAs广泛存在于菊科、豆科、紫草科的多种药用植物中。《中国药典》2020年版共收载含有PAs的药材8种,包括千里光Senecionis Scandentis Herba、款冬花Farfarae Flos、佩兰Eupatorii Herba、紫草Arnebiae Radix等,涉及成方制剂数十种。此外,《卫生部药品标准》《药品注册标准》等收载含PAs制剂尚有200余种。除千里光药材外,其他含PAs中药及其制剂均没有关于PAs类成分的安全限量标准,其临床用药安全存在极大的风险。对含PAs中成药的研究概况进行了系统总结、分析,以期为此类中成药的临床用药安全提供警示和参考。 相似文献
7.
目的评价市售吴茱萸EuodiaeFructus的质量并研究不同商品规格吴茱萸中化学成分与肝细胞毒性的相关性,为吴茱萸全面质量控制提供依据。方法按吴茱萸药材商品规格收集小花吴茱萸7批,中花吴茱萸22批,大花吴茱萸10批,建立了UPLC法同时测定吴茱萸中柠檬苦素(limonin,LIM)、吴茱萸碱(evodiamine,EVD)、吴茱萸次碱(rutaecarpine,RUT)、 1-甲基-2-壬基-4-(1H)-喹诺酮[1-methyl-2-nonyl-4(1H)-quinolone, MNQ]、 1-甲基-2-十一烷基-4(1H)-喹诺酮[1-methyl-2-undecyl-4(1H)-quinolone,MUQ]和吴茱萸新碱(evocarpine,EVC)的含量;采用CCK-8法检测吴茱萸对L02肝细胞的生长抑制作用。运用SIMCA-P 14.1统计软件对吴茱萸的细胞存活率进行主成分分析(principal component analysis,PCA)。结果有19批商品符合《中国药典》2020年版规定,不符合药典要求的20批样品中有10批为药材基原不符,有1批EVD和RUT的总量不符合药典规定,9批LIM含量不符合药典规定。7批小花吴茱萸中1批不符合药典要求,22批中花吴茱萸中10批不符合药典要求,10批大花吴茱萸中9批不符合药典要求。同时发现小花吴茱萸中LIM含量高于中花和大花吴茱萸,而生物碱含量中花和大花吴茱萸中较高。其中S33~S39样品按果实大小属于中花吴茱萸但不含LIM,将其称为中花样吴茱萸劣品。基于建立的UPLC方法同时测定吴茱萸中LIM和5种生物碱含量;PCA分析模型将小花吴茱萸、中花吴茱萸、大花吴茱萸和中花样吴茱萸劣品的毒性很好地区分为4个区域,对L02肝细胞的生长抑制作用为中花样吴茱萸劣品大花吴茱萸中花吴茱萸小花吴茱萸,且LIM与5种生物碱的比值和吴茱萸对L02肝细胞的半数抑制率(IC_(50))总体上呈正相关。结论吴茱萸的毒性与LIM和5种生物碱比例有关,LIM与5种生物碱含量和的比值越大,吴茱萸样品毒性越小。提示大花吴茱萸不适合作为商品流通,同时吴茱萸质量控制应考虑药材中LIM和生物碱类成分含量的比例。 相似文献
8.
目的对苎叶蒟Piper boehmeriifolium的枝叶部位进行化学成分研究。方法采用硅胶、RP-C_(18)柱色谱、Sephadex LH-20凝胶柱色谱和半制备HPLC等方法进行分离和纯化,并综合运用IR、HR-ESI-MS、~1H-NMR、~(13)C-NMR、DEPT、HSQC、HMBC等方法鉴定化合物的结构。结果从苎叶蒟乙醇提取物中分离得到15个化合物,分别鉴定为3-(3,4-methylenedioxybenzyl)-4-(3,4-dimethoxybenzyl)-1H-pyrrole-2,5-dione(1)、2E,4E-decadienoylpiperidide(2)、2E-decenoylpiperidide(3)、墙草碱(4)、piperchabamide B(5)、假蒟亭碱(6)、piperdardine(7)、胡椒新碱(8)、胡椒碱(9)、二氢荜茇明宁碱(10)、chingchengenamide A(11)、假荜茇酰胺B(12)、guineensine(13)、荜茇宁(14)和kusunokinin(15)。结论化合物1为新化合物,命名为胡椒木脂酰亚胺,化合物2、3、7、8、10和15为首次从该植物中分离得到。 相似文献
9.
10.
Pavan Kumar Sagar S. Pandit Anke Steppuhn Ian T. Baldwin 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(4):1245-1252
Manduca sexta (Ms) larvae are known to efficiently excrete ingested nicotine when feeding on their nicotine-producing native hostplant, Nicotiana attenuata. Here we describe how ingested nicotine is co-opted for larval defense by a unique mechanism. Plant-mediated RNAi was used to silence a midgut-expressed, nicotine-induced cytochrome P450 6B46 (CYP6B46) in larvae consuming transgenic N. attenuata plants producing MsCYP6B46 dsRNA. These and transgenic nicotine-deficient plants were planted into native habitats to study the phenotypes of larvae feeding on these plants and the behavior of their predators. The attack-behavior of a native wolf spider (Camptocosa parallela), a major nocturnal predator, provided the key to understanding MsCYP6B46’s function: spiders clearly preferred CYP6B46-silenced larvae, just as they had preferred larvae fed nicotine-deficient plants. MsCYP6B46 redirects a small amount (0.65%) of ingested nicotine from the midgut into hemolymph, from which nicotine is exhaled through the spiracles as an antispider signal. CYP6B46-silenced larvae were more susceptible to spider-attack because they exhaled less nicotine because of lower hemolymph nicotine concentrations. CYP6B46-silenced larvae were impaired in distributing ingested nicotine from midgut to hemolymph, but not in the clearing of hemolymph nicotine or in the exhalation of nicotine from hemolymph. MsCYP6B46 could be a component of a previously hypothesized pump that converts nicotine to a short-lived, transportable, metabolite. Other predators, big-eyed bugs, and antlion larvae were insensitive to this defense. Thus, chemical defenses, too toxic to sequester, can be repurposed for defensive functions through respiration as a form of defensive halitosis, and predators can assist the functional elucidation of herbivore genes.Plants produce a pharmacopeia of potent chemical defenses that prevent the attack of unadapted herbivores and thwart the growth of adapted ones. Frequently, lepidopteran herbivores co-opt these diet-acquired toxins for their own defensive purposes. The eastern tent caterpillar (Malacosoma americanum) regurgitates hydrogen cyanide and benzaldehyde ingested from their cyanogenic hostplants when attacked by ants (1). The Atala butterfly (Eumaeus atala) acquires a toxic azoxyglycoside from its cycad hosts and becomes unpalatable to bird and ant predators (2). Similarly, rattlebox moths (Utetheisa ornatrix) co-opt pyrrolizidine alkaloids that their larvae sequester while feeding on rattlebox legume hostplants (Crotalaria spp.) to deter predatory spiders (3). Prey frequently advertise their toxic status with warning colorations, odors, and behaviors, and predators readily learn these aposematic signals to avoid consuming toxic prey (4). The molecular mechanisms of how herbivores co-opt plant defenses for their own defense remain largely unexplored.The pyridine alkaloid nicotine is a defense metabolite of several Nicotiana spp. Nicotine is extremely effective against herbivores because of its ability to poison the essential neuromuscular junction common to all animals that use muscles to move: the acetylcholine receptor (5, 6). Nicotiana spp. hostplants respond to the herbivore attack with large increases in nicotine accumulation (7). However, the tobacco hornworm (Manduca sexta, Ms), a specialist lepidopteran herbivore that feeds on nicotine-producing Nicotiana plants, tolerates doses of nicotine that are lethal for unadapted herbivores (8). More endoparasitoid wasps (Cotesia congregata) emerged as adults from parasitized M. sexta larvae fed on low nicotine varieties of cultivated tobacco than from larvae fed on nicotine-rich varieties (9). The generalist predatory argentine ant (Iridomyrmex humilis) also preferred M. sexta larvae reared on artificial diets (AD) without nicotine over those reared on high nicotine diets, and were deterred by topical nicotine treatments (10). These results suggest that M. sexta larvae might be able to use this diet-derived toxin for their own protection. How this happens remains a mystery, as the larvae’s resistance of ingested nicotine does not appear to include sequestration and storage of this toxin.The exact mechanisms responsible for M. sexta’s nicotine resistance remain unclear, but both efficient excretion and metabolism appear to be involved. Some researchers have focused on the polar metabolites of nicotine, such as cotinine and the N-oxides of both nicotine and cotinine, which are commonly found in the urine and blood of human smokers (8, 11, 12); cytochrome P450s (CYPs) are thought to mediate nicotine’s oxidation to these metabolites (8, 11, 13–15), but other researchers have been unable to find the oxides in M. sexta’s excretions and propose that nicotine is rapidly excreted without modification (16–18). Although this theory is widely accepted, most studies have not been able to recover all of the ingested nicotine in the frass and nicotine can be found in the hemolymph of larvae feeding on nicotine-containing diets. Hence, within these physiological limits of M. sexta’s excretory-based tolerance lie opportunities for the defensive use of nicotine. Whether nicotine-resistance and co-option are regulated by a common mechanism remains unknown.Here we examine how M. sexta larvae co-opt diet-ingested nicotine for their own defense. In a previous unbiased microarray study, we found that a midgut-expressed cytochrome P450 (CYP6B46) was strongly down-regulated in larvae that were fed genetically modified hostplants with suppressed nicotine production (19, 20). To evaluate if this CYP6B46 is involved in nicotine resistance and co-option, we used a reverse genetics approach, plant-mediated RNA interference (PMRi) (20, 21), to silence this gene in larvae feeding on nicotine-containing, native coyote tobacco (Nicotiana attenuata) hostplants transformed to harbor the silencing construct. Lepidopteran herbivores appear to lack the RNA-dependent RNA polymerase required to sustain gene silencing by RNAi; however, a continuous supply of double-stranded (ds)RNA administered via the hostplant (or diet) effectively silences genes in these herbivores (21, 22).N. attenuata plants were transformed with an expression vector containing a 300-bp fragment of CYP6B46 in an inverted repeat (ir) orientation. Continuous dsRNA ingestion efficiently silenced CYP6B46 in the midguts of larvae feeding on these plants in a highly target-sequence–specific manner, as the most similar CYP expressed in larval midguts, CYP6B45, was not cosilenced (20). These PMRi plants were planted into the native habitat of both hostplant and larvae, the Great Basin Desert, Utah, which teems with larval predators—such as bugs, mantids, ants, antlions, spiders, and lizards—but lacks the Argentine ants and C. congregata endoparasitoids previously reported to be nicotine-sensitive. One of these predators, a wolf spider [Camptocosa parallela (Lycosidae)], selectively attacked CYP6B46-silenced larvae just as it did larvae feeding on nicotine-free hostplants. The particular predatory behavior of these spiders revealed the function of MsCYP6B46 in externalizing ingested nicotine for defensive use. The combination of natural history studies and the plant- and herbivore-reverse genetic procedures can fruitfully dissect the molecular mechanisms governing the tritrophic interactions. 相似文献