全文获取类型
收费全文 | 760篇 |
免费 | 60篇 |
专业分类
耳鼻咽喉 | 7篇 |
儿科学 | 15篇 |
妇产科学 | 18篇 |
基础医学 | 95篇 |
口腔科学 | 5篇 |
临床医学 | 73篇 |
内科学 | 124篇 |
皮肤病学 | 19篇 |
神经病学 | 39篇 |
特种医学 | 18篇 |
外科学 | 76篇 |
综合类 | 10篇 |
预防医学 | 42篇 |
眼科学 | 43篇 |
药学 | 85篇 |
中国医学 | 76篇 |
肿瘤学 | 75篇 |
出版年
2021年 | 7篇 |
2019年 | 21篇 |
2018年 | 17篇 |
2017年 | 13篇 |
2016年 | 7篇 |
2015年 | 7篇 |
2014年 | 8篇 |
2013年 | 18篇 |
2012年 | 25篇 |
2011年 | 25篇 |
2010年 | 11篇 |
2009年 | 13篇 |
2008年 | 20篇 |
2007年 | 20篇 |
2006年 | 20篇 |
2005年 | 28篇 |
2004年 | 33篇 |
2003年 | 35篇 |
2002年 | 33篇 |
2001年 | 30篇 |
2000年 | 29篇 |
1999年 | 21篇 |
1998年 | 11篇 |
1996年 | 10篇 |
1995年 | 8篇 |
1993年 | 9篇 |
1992年 | 23篇 |
1991年 | 24篇 |
1990年 | 23篇 |
1989年 | 13篇 |
1988年 | 24篇 |
1987年 | 14篇 |
1986年 | 15篇 |
1985年 | 10篇 |
1984年 | 14篇 |
1983年 | 16篇 |
1982年 | 11篇 |
1981年 | 6篇 |
1980年 | 7篇 |
1979年 | 15篇 |
1978年 | 10篇 |
1977年 | 9篇 |
1975年 | 8篇 |
1974年 | 17篇 |
1973年 | 7篇 |
1972年 | 6篇 |
1971年 | 8篇 |
1969年 | 8篇 |
1968年 | 8篇 |
1967年 | 6篇 |
排序方式: 共有820条查询结果,搜索用时 15 毫秒
1.
Xing Zheng Jiang Du Yunlong Xu Duanfang Liao George R. Pettit 《Medicinal chemistry research》2010,19(4):337-343
Two cancer cell growth inhibitory esters, 1,2-dipalmitoyl-3-glucosyl glycerol (1) and 1,6-dihydroxy-hexane-bis-palmitoyl ester (2), together with arachidic acid-2-hydroxy-glycerol ester, daucosterol, and oleanolic acid, were isolated from the roots of
Peucedanum ledebourielloides (Apiaceae family). The structures were determined by spectroscopic analyses. The esters 1 and 2 displayed significant activity against the SGC-7901, HT-29, and HL-60 cancer cell lines. 相似文献
2.
Dolastatin 10, a cytostatic peptide containing several unique amino acid subunits, was isolated from the marine shell-less mollusk Dolabella auricularia (Pettit GR, Kamano Y, Herald CL, Tuinman AA, Boettner FE, Kizu H, Schmidt JM, Baczynskyj L, Tomer KB and Bontems RJ, J Am Chem Soc 109: 6883-6885, 1987). Since our preliminary studies demonstrated that dolastatin 10 inhibited tubulin polymerization and the binding of radiolabeled vinblastine to tubulin, an initial characterization of the properties of dolastatin 10 included a comparison to other antimitotic drugs interfering with vinca alkaloid binding to tubulin (vinblastine, maytansine, rhizoxin, and phomopsin A). Dolastatin 10 inhibited the growth of L1210 murine leukemia cells in culture, with a concordant rise in the mitotic index, and its IC50 value for cell growth was 0.5 nM. Comparable values for the other drugs were 0.5 nM for maytansine, 1 nM for rhizoxin, 20 nM for vinblastine, and 7 microM for phomopsin A. IC50 values were also obtained for the polymerization of purified tubulin in glutamate: 1.2 microM for dolastatin 10, 1.4 microM for phomopsin A, 1.5 microM for vinblastine, 3.5 microM for maytansine, and 6.8 microM for rhizoxin. Dolastatin 10 and vinblastine were comparable in their effects on microtubule assembly dependent on microtubule-associated proteins. Preliminary studies indicated that dolastatin 10, like vinblastine, causes formation of a cold-stable tubulin aggregate at higher drug concentrations. We confirmed that rhizoxin, phomopsin A, and maytansine also inhibit the binding of radiolabeled vinblastine and vincristine to tubulin. Dolastatin 10 and phomopsin A were the strongest inhibitors of these reactions, and rhizoxin the weakest. Dolastatin 10, phomopsin A, maytansine, vinblastine, and rhizoxin all inhibited tubulin-dependent GTP hydrolysis. The greatest inhibition of hydrolysis was observed with dolastatin 10 and phomopsin A, and the least inhibition with rhizoxin. 相似文献
3.
Eighteen configurational isomers of the antimitotic peptide dolastatin 10 (Bai et al., Biochem Pharmacol 39: 1941-1949, 1990) derived from Dolabella auricularia, together with segments obtained as precursors in its synthesis (Pettit et al., J Am Chem Soc 111: 5463-5465, 1989), were examined as inhibitors of tubulin polymerization and as inhibitors of growth of L1210 murine leukemia cells in culture. Dolastatin 10 consists of four amino acids (in order from the amino terminus: dolavaline, valine, dolaisoleucine, and dolaproine), three unique to D. auricularia, linked to an unusual primary amine (dolaphenine, probably derived from phenylalanine) at what would otherwise be its carboxyl terminus. Dolastatin 10 has nine asymmetric carbon atoms, and available isomers included alternate configurations at five positions (positions 9 and 10 in the dolaproine moiety and positions 18, 19 and 19a in the dolaisoleucine moiety). For tubulin polymerization, only alterations at positions 18 and 19 resulted in loss of inhibitory activity of the isomer. In addition, a tripeptide containing dolavaline, valine and dolaisoleucine with all asymmetric carbons identical configurationally to those in dolastatin 10 was found to be about 30% as effective as dolastatin 10 in inhibiting tubulin polymerization. Cytotoxic effects were much more sensitive to alterations in the dolastatin 10 structure. The only modification which did not lead to reduced cytotoxicity was reversal of configuration at position 19a in the dolaisoleucine moiety. Both this isomer and dolastatin 10 had IC50 values of less than 1 nM. Several other isomers had IC50 values with the L1210 cells in the range of 30-90 nM, but these did not correlate well with their inhibitory effects on tubulin polymerization. The tripeptide effective as an inhibitor of tubulin polymerization had no activity against the L1210 cells. 相似文献
4.
Background and Objective: Although the empirical characteristics of ArF excimer laser corneal ablation have been well documented, the exact ablation mechanisms are not well understood. The present paper reports a quantitative analysis of corneal ablation plumes using in situ time resolved laser light scattering and Raman spectroscopy. Study Design/Materials and Methods: Bovine corneas were used as the ArF excimer laser ablation targets. Light scattering data were recorded from the ablation plume as a function of height above the tissue surface and as function of delay time with respect to the ablative ArF laser pulse. Results: Raman spectra of the ablation plume allow identification of the particles as water. Mean plume particle diameters are found to decrease with height, while the particle volume fractions are relatively constant. The total volume of plume particles correlates well with the total volume of water in the ablated corneal tissue. Conclusion: The finding of a non-evolving plume composed of water spherules, combined with the excellent agreement between total volume of water in the plume and the content of water in the ablated corneal tissue, support the concept of photodecomposition or “cold ablation” for corneal tissue during ArF excimer laser ablation. © 1995 Wiley-Liss, Inc. 相似文献
5.
M. N. Ediger G. H. Pettit R. P. Weiblinger C. H. Chen 《Lasers in surgery and medicine》1993,13(2):204-210
The time-resolved transmission of collagen films and 10-μm sections of bovine cornea during ArF laser ablation has been investigated. The film studies were performed on thin layers of extracted bovine corneal collagen, the principal chromophore in 193 nm photoablation. Transmission measurements were made on both dry and water-saturated films to assess the sensitivity of the ablation process to hydration. Distinct transient optical changes were observed in both fully desiccated and rehydrated films. Dehydrated films exhibit rapid reduction in film absorption over the time-course of the ablating laser pulse, presumably due to chromophore bleaching or annihilation. In contrast, rehydrated films demonstrate a short-lived enhancement of the attenuation. In either case, a single ablative laser pulse increased the long-term transmission of the film, although this increase was a factor of five greater for dehydrated films than for rehydrated samples. Results obtained from corneal tissue sections were essentially identical to those derived from hydrated collagen films. © 1993 Wiley-Liss, Inc. 相似文献
6.
M W Miller M Azadniv S E Pettit C C Church E L Carstensen D Hoffman 《Ultrasound in medicine & biology》1989,15(3):255-262
This study was undertaken in an attempt to determine a physical mechanism of action for a recently published report of a small but statistically significant increase in sister chromatid exchanges (SCEs) in Chinese hamster ovary cells exposed to high-intensity pulsed ultrasound. The "positive" report's protocol involved a sizeable chance of ultrasound beam impingement on the side wall of the cell exposure chamber. Ten experiments per regimen were conducted; the regimens included exposures of (a) chamber center, (b) chamber wall, (c) nine grid sites, 0.5 mm between sites, and (d) nine grid sites, 1.5 mm between sites. The last was an exact replication of the conditions previously reported to induce the small SCE effect. The results did not support the postulate of an increase in SCEs with the ultrasound exposures. 相似文献
7.
J A Ferry C K Pettit A E Rosenberg N L Harris 《American journal of clinical pathology》1991,96(5):577-581
When fungi infect the bone marrow, typically they are associated with granuloma formation and/or necrosis, and the fungi are found within histiocytes or admixed with necrotic debris. Recently two bone marrow biopsy specimens were encountered in which fungi were confined to the cytoplasm of megakaryocytes, a finding not previously reported in the literature. The first case was that of a 46-year-old man with pulmonary histoplasmosis and no known immunodeficiency. The second was that of a 38-year-old man with the acquired immune deficiency syndrome and cryptococcal meningitis. In the first case, many megakaryocytes contained fungal forms consistent with Histoplasma. In the second, one small cluster of megakaryocytes contained several budding yeast consistent with Cryptococcus. Neither marrow biopsy specimen had necrosis, granulomas, or histiocytic infiltration. In both cases, because of the unusual localization of the fungi, they were initially overlooked. The bone marrow may contain fungi even in the absence of abnormalities suggesting fungal infection on routinely stained sections. A silver stain or a periodic acid--Schiff stain should be performed on all marrow biopsy specimens in cases of known or suspected fungal infection outside the marrow. The phenomenon of megakaryocyte emperipolesis is well known, and this process may be responsible for the apparent ability of megakaryocytes to internalize fungi. 相似文献
8.
Phenotypic modulation of gonococcal lipooligosaccharide in acidic and alkaline culture. 总被引:2,自引:2,他引:2 下载免费PDF全文
Neisseria gonorrhoeae infects a diverse array of niches in its human host, which expose the organism to dramatic variations in pH. We examined growth and lipooligosaccharide expression of two gonococcal strains in liquid and solid cultures under acidic, neutral, and alkaline conditions. Growth rates in broth were similar under the three conditions, and the pH remained fairly constant throughout the growth cycle. Altered lipooligosaccharide expression at the different pHs was noted in both plate- and broth-grown organisms. 相似文献
9.
N. W. Davies A. I. Pettit R. Agarwal N. B. Standen 《Pflügers Archiv : European journal of physiology》1991,419(1):25-31
We have examined the effects of 4-aminopyridine (4-AP) on single ATP-dependent potassium channels in patches excised from frog skeletal muscle. 4-AP applied to the internal face of the membrane caused a flickery block. We could not detect any flickery block when 10 mM 4-AP was applied to the external surface of the membrane. The reduction in mean unitary current by internal 4-AP was consistent with 11 binding with a K
d of 3.3 mM at 0 mV. The block was voltage-dependent, increasing with depolarization with an effective valency of 0.57. Rate constants for blocking and unblocking by 4-AP were obtained by fitting functions to the distribution of current amplitudes. Both rate constants were voltage-dependent. At 0 mV they were 17 mM–1 ms–1 and 61 ms–1. Simulation of the block using these rate constants produced a flickery block very similar to that observed experimentally. 相似文献
10.
Isoguanine (2) was found to be an antineoplastic constituent of Prioneris thestylis Dbldy. wings. Three other purine components of the butterfly wings were identified as hypoxanthine (3), uric acid (4) and xanthine (5). Isolation of urocanic acid (6) from the same wing material represented the first detection of this interesting histidine derivative in an arthropod. 相似文献