全文获取类型
收费全文 | 2457篇 |
免费 | 165篇 |
国内免费 | 58篇 |
专业分类
耳鼻咽喉 | 7篇 |
儿科学 | 5篇 |
妇产科学 | 11篇 |
基础医学 | 138篇 |
口腔科学 | 1082篇 |
临床医学 | 55篇 |
内科学 | 222篇 |
皮肤病学 | 17篇 |
神经病学 | 73篇 |
特种医学 | 23篇 |
外科学 | 57篇 |
综合类 | 214篇 |
预防医学 | 171篇 |
眼科学 | 12篇 |
药学 | 519篇 |
中国医学 | 39篇 |
肿瘤学 | 35篇 |
出版年
2024年 | 3篇 |
2023年 | 30篇 |
2022年 | 31篇 |
2021年 | 139篇 |
2020年 | 75篇 |
2019年 | 63篇 |
2018年 | 63篇 |
2017年 | 67篇 |
2016年 | 87篇 |
2015年 | 96篇 |
2014年 | 155篇 |
2013年 | 182篇 |
2012年 | 143篇 |
2011年 | 192篇 |
2010年 | 144篇 |
2009年 | 115篇 |
2008年 | 101篇 |
2007年 | 116篇 |
2006年 | 84篇 |
2005年 | 91篇 |
2004年 | 64篇 |
2003年 | 63篇 |
2002年 | 52篇 |
2001年 | 56篇 |
2000年 | 33篇 |
1999年 | 40篇 |
1998年 | 40篇 |
1997年 | 27篇 |
1996年 | 28篇 |
1995年 | 23篇 |
1994年 | 30篇 |
1993年 | 23篇 |
1992年 | 36篇 |
1991年 | 19篇 |
1990年 | 12篇 |
1989年 | 18篇 |
1988年 | 11篇 |
1987年 | 13篇 |
1986年 | 18篇 |
1985年 | 15篇 |
1984年 | 16篇 |
1983年 | 7篇 |
1982年 | 13篇 |
1981年 | 11篇 |
1980年 | 9篇 |
1979年 | 7篇 |
1978年 | 5篇 |
1977年 | 5篇 |
1976年 | 5篇 |
1975年 | 2篇 |
排序方式: 共有2680条查询结果,搜索用时 203 毫秒
1.
2.
《Journal of Pharmaceutical Analysis》2022,12(2):221-231
Breast cancer is one of the leading causes of cancer-related deaths in women worldwide. It is a cancer that originates from the mammary ducts and involves mutations in multiple genes. Recently, the treatment of breast cancer has become increasingly challenging owing to the increase in tumor heterogeneity and aggressiveness, which gives rise to therapeutic resistance. Epidemiological, population-based, and hospital-based case-control studies have demonstrated an association between high intake of certain Allium vegetables and a reduced risk in the development of breast cancer. Diallyl disulfide (DADS) and diallyl trisulfide (DATS) are the main allyl sulfur compounds present in garlic, and are known to exhibit anticancer activity as they interfere with breast cancer cell proliferation, tumor metastasis, and angiogenesis. The present review highlights multidrug resistance mechanisms and their signaling pathways in breast cancer. This review discusses the potential anticancer activities of DADS and DATS, with emphasis on drug resistance in triple-negative breast cancer (TNBC). Understanding the anticancer activities of DADS and DATS provides insights into their potential in targeting drug resistance mechanisms of TNBC, especially in clinical studies. 相似文献
3.
Abstract: Native chemical ligation has proven to be a powerful method for the synthesis of small proteins and the semisynthesis of larger ones. The essential synthetic intermediates, which are C‐terminal peptide thioesters, cannot survive the repetitive piperidine deprotection steps of Nα‐9‐fluorenylmethoxycarbonyl (Fmoc) chemistry. Therefore, peptide scientists who prefer to not use Nα‐t‐butyloxycarbonyl (Boc) chemistry need to adopt more esoteric strategies and tactics in order to integrate ligation approaches with Fmoc chemistry. In the present work, side‐chain and backbone anchoring strategies have been used to prepare the required suitably (partially) protected and/or activated peptide intermediates spanning the length of bovine pancreatic trypsin inhibitor (BPTI). Three separate strategies for managing the critical N‐terminal cysteine residue have been developed: (i) incorporation of Nα‐9‐fluorenylmethoxycarbonyl‐S‐(N‐methyl‐N‐phenylcarbamoyl)sulfenylcysteine [Fmoc‐Cys(Snm)‐OH], allowing creation of an otherwise fully protected resin‐bound intermediate with N‐terminal free Cys; (ii) incorporation of Nα‐9‐fluorenylmethoxycarbonyl‐S‐triphenylmethylcysteine [Fmoc‐Cys(Trt)‐OH], generating a stable Fmoc‐Cys(H)‐peptide upon acidolytic cleavage; and (iii) incorporation of Nα‐t‐butyloxycarbonyl‐S‐fluorenylmethylcysteine [Boc‐Cys(Fm)‐OH], generating a stable H‐Cys(Fm)‐peptide upon cleavage. In separate stages of these strategies, thioesters are established at the C‐termini by selective deprotection and coupling steps carried out while peptides remain bound to the supports. Pilot native chemical ligations were pursued directly on‐resin, as well as in solution after cleavage/purification. 相似文献
4.
5.
SEVERO SALVADORI REMO GUERRINI PIERO ANDREA BOREA ROBERTO TOMATIS 《Chemical biology & drug design》1992,40(5):437-444
The synthesis of pseudotetrapeptides H-Tyr-D-Ala-Phe-NH-(CH2)2-NH2 (1a), H-Tyr-D-Ala-Phe-ψ(CH2-NH)-Gly-NH2 (2a), H-Tyr-D-Ala-ψ(CH2-NH)-Phe-Gly-NH2 (3a), and H-Tyr-ψ(CH2-NH)-D-Ala-Phe-Gly-NH2 (4a), representing the N-terminal tetrapeptide sequence of dermorphin, in which amide bonds are replaced by CH2-NH bond, is described. N-acetyl-Tyr and desamino-Tyr pseudopeptide analogs (1-4b), (1-3c) are also described. The analogs were assayed in binding studies based on displacement of μ and δ-receptor selective radiolabels from rat brain membrane and in a bioassay using guinea pig ileum (GPI). Pseudopeptides in which the C-terminal (1a) or D-Ala-Phe (3a) amide bond are substituted, exhibit higher μ-affinities and μ-receptor selectivity than the corresponding Phe-Gly or Tyr-D-Ala analogs (2a, 4a). Acetyl-and desamino-Tyr pseudopeptide analogs (1-4b) and (1-3c) did not exhibit μ and δ-opioid receptor affinity at nM concentration. The relevance of the single peptide replacement and of its association to acetylation or amino group elimination of Tyr, is discussed on the basis of a receptor model for μ and δ opioids. 相似文献
6.
The previously described cyclic delta opioid receptor-selective tetrapeptide H-Tyr-d -Cys-Phe-d -Pen-OH (JOM-13) was modified at residue 3 by incorporation of both natural and unnatural amino acids with varying steric, electronic, and lipophilic properties. Effects on mu and delta opioid receptor binding affinities were evaluated by testing the compounds for displacement of radiolabeled receptor-selective ligands in a guinea pig brain receptor binding assay. Results obtained with the bulky aromatic 1-Nal3 and 2-Nal3 substitutions suggest that the shape of the receptor subsite with which the side chain of the internal aromatic residue interacts differs for delta and mu receptors. This subsite of either receptor can accommodate the transverse steric bulk of the 1-Nal3 side chain but only the delta receptor can readily accept the more elongated 2-Nal3 side chain. Several analogs with pi-excessive heteroaromatic side chains in residue 3 were examined. In general, these analogs display diminished binding to mu and delta receptors, consistent with previous findings for analogs with residue 3 substitutions of modified electronic character. Several analogs with alkyl side chains in residue 3 were also examined. While delta receptor binding affinity is severely diminished with Val3, Ile3, and Leu3 substitutions, Cha3 substitution is very well tolerated, indicating that, contrary to the widely held belief, an aromatic side chain in this portion of the ligand is not required for delta receptor binding. Where possible, comparison of results in this delta-selective tetrapeptide series with those reported for analogous modification in the cyclic delta-selective pentapeptide [d -Pen2, d -Pen5]enkephalin (DPDPE) and linear pentapeptide enkephalins reveals similar trends. 相似文献
7.
CHRISTIANE MENDRE VERONIQUE SARRADE BERNARD CALAS 《Chemical biology & drug design》1992,39(3):278-284
The continuous flow syntheses of endothelin 1, proendothelin 2. ATP binding site of the CDC2 kinase 3, and fragment 18-30 of an actin 4, have been performed by using a polyacrylamide gel resin Expansin? (about 0.6 mmol NH2/g) with the glycolamidic ester handle as labile anchorage. In addition, we report here a method of air oxidation which reduces the formation of side-products related to the formation of intermolecular disulfide bridges. 相似文献
8.
用酸蚀法提高纯钛与光固化冠桥树脂粘结强度的研究 总被引:5,自引:1,他引:4
目的:研究用酸蚀法提高钛与光固化复合树脂剪切粘结强度的可行性,并观察表面粗糙度与剪切粘结强度之间的关系。方法:采用不同浓度的酸蚀剂对钛铸件表面进行酸蚀,并与artglass光固化复合树脂进行粘结,以单纯喷砂组为对照,比较剪切粘结强度的差异。对酸蚀后及剪切试验后的金属表面进行扫描电镜观察,并测定其表面粗糙度。结果:用酸蚀法可以显著提高钛与复合树脂的粘结强度,HF浓度为4%时粘结强度最高。表面粗糙度随酸蚀剂的浓度增高而下降。结论:纯钛铸件用酸蚀法处理后可以获得较高的粘结强度,HF酸浓度以4%为宜。表面粗糙度对粘结强度不起决定性作用。 相似文献
9.
用神经网络法预测药物在体透过人皮肤的渗透性 总被引:4,自引:2,他引:2
傅旭春 《浙江大学学报(医学版)》2003,32(2):152-154,158
目的:预测药物在体透过人皮肤的渗透性。方法:以正辛醇/水分配系数(logP)、分子体积(V)、氢键酸度(∑β2^H)和氢键碱度(∑β2^H)等理化参数作为输入层神经元,以药物在一定时间内在体透过人皮肤的透过比的对数值(R,透过量/未透过量)作为输出层神经元,建立起合适的BP(Back—propagation)神经网络。结果:17个药物在一定时间内在体透过人皮肤的透过比的神经网络计算值和实测值均相当符合。结论:用BP神经网络法可以较好地预测药物在体透过人皮肤的渗透性。 相似文献
10.
Peter E. Jensen 《Seminars in immunology》1995,7(6)
CD4+ helper T cells recognize short peptides stably associated with class II MHC molecules displayed on the surface of antigen presenting cells. Very little is known about the sequence of events that lead to the generation of these peptides from protein antigens. It is likely that native proteins must partially unfold before they are cleaved by endopeptidases or bind to MHC proteins. For many antigens, the rate-limiting step in unfolding may involve reduction of disulfide bonds. Evidence that disulfide reduction occurs in endocytic compartments is reviewed and potential mechanisms for the reduction of antigen disulfide bonds are proposed. 相似文献