全文获取类型
收费全文 | 2975篇 |
免费 | 95篇 |
国内免费 | 3篇 |
专业分类
化学 | 2358篇 |
晶体学 | 15篇 |
力学 | 31篇 |
数学 | 304篇 |
物理学 | 365篇 |
出版年
2023年 | 18篇 |
2022年 | 77篇 |
2021年 | 100篇 |
2020年 | 74篇 |
2019年 | 54篇 |
2018年 | 55篇 |
2017年 | 49篇 |
2016年 | 121篇 |
2015年 | 113篇 |
2014年 | 112篇 |
2013年 | 193篇 |
2012年 | 210篇 |
2011年 | 290篇 |
2010年 | 184篇 |
2009年 | 137篇 |
2008年 | 200篇 |
2007年 | 151篇 |
2006年 | 152篇 |
2005年 | 148篇 |
2004年 | 80篇 |
2003年 | 80篇 |
2002年 | 81篇 |
2001年 | 33篇 |
2000年 | 19篇 |
1999年 | 39篇 |
1998年 | 32篇 |
1997年 | 23篇 |
1996年 | 23篇 |
1995年 | 15篇 |
1994年 | 10篇 |
1993年 | 10篇 |
1992年 | 17篇 |
1991年 | 7篇 |
1990年 | 9篇 |
1989年 | 11篇 |
1988年 | 9篇 |
1987年 | 8篇 |
1986年 | 10篇 |
1985年 | 8篇 |
1984年 | 16篇 |
1983年 | 5篇 |
1982年 | 5篇 |
1981年 | 10篇 |
1980年 | 5篇 |
1979年 | 6篇 |
1978年 | 6篇 |
1977年 | 10篇 |
1976年 | 7篇 |
1974年 | 7篇 |
1973年 | 5篇 |
排序方式: 共有3073条查询结果,搜索用时 15 毫秒
111.
Synthesis and Biological Evaluation of RGD Peptidomimetic–Paclitaxel Conjugates Bearing Lysosomally Cleavable Linkers
下载免费PDF全文
![点击此处可从《Chemistry (Weinheim an der Bergstrasse, Germany)》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Alberto Dal Corso Dr. Michele Caruso Dr. Laura Belvisi Dr. Daniela Arosio Prof. Dr. Umberto Piarulli Dr. Clara Albanese Dr. Fabio Gasparri Dr. Aurelio Marsiglio Dr. Francesco Sola Dr. Sonia Troiani Dr. Barbara Valsasina Dr. Luca Pignataro Dr. Daniele Donati Prof. Dr. Cesare Gennari 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(18):6921-6929
Two small‐molecule–drug conjugates (SMDCs, 6 and 7 ) featuring lysosomally cleavable linkers (namely the Val–Ala and Phe–Lys peptide sequences) were synthesized by conjugation of the αvβ3‐integrin ligand cyclo[DKP–RGD]‐CH2NH2 ( 2 ) to the anticancer drug paclitaxel (PTX). A third cyclo[DKP–RGD]–PTX conjugate with a nonpeptide “uncleavable” linker ( 8 ) was also synthesized to be tested as a negative control. These three SMDCs were able to inhibit biotinylated vitronectin binding to the purified αVβ3‐integrin receptor at nanomolar concentrations and showed good stability at pH 7.4 and pH 5.5. Cleavage of the two peptide linkers was observed in the presence of lysosomal enzymes, whereas conjugate 8 , which possesses a nonpeptide “uncleavable” linker, remained intact under these conditions. The antiproliferative activities of the conjugates were evaluated against two isogenic cell lines expressing the integrin receptor at different levels: the acute lymphoblastic leukemia cell line CCRF‐CEM (αVβ3?) and its subclone CCRF‐CEM αVβ3 (αVβ3+). Fairly effective integrin targeting was displayed by the cyclo[DKP–RGD]–Val–Ala–PTX conjugate ( 6 ), which was found to differentially inhibit proliferation in antigen‐positive CCRF‐CEM αVβ3 versus antigen‐negative isogenic CCRF‐CEM cells. The total lack of activity displayed by the “uncleavable” cyclo[DKP–RGD]–PTX conjugate ( 8 ) clearly demonstrates the importance of the peptide linker for achieving the selective release of the cytotoxic payload. 相似文献
112.
113.
Vanessa F. M. Carvalho Daniela V. Giacone Leticia V. Costa‐Lotufo Edilberto Rocha Silveira Luciana B. Lopes 《Biomedical chromatography : BMC》2019,33(2)
This study reports the development of a simple and reproducible method, with high rates of recovery, to extract the cytotoxic agent piplartine from skin layers, and a sensitive and rapid UV‐HPLC method for its quantification. Considering the potential of piplartine for topical treatment of skin cancer, this method may find application for formulation development and pharmacokinetics studies to assess cutaneous bioavailability. Porcine skin was employed as a model for human tissue. Piplartine was extracted from the stratum corneum (SC) and remaining viable skin layers (VS) using methanol, vortex homogenization and bath sonication, and subsequently assayed by HPLC using a C18 column, and 1:1 (v/v) acetonitrile–water (adjusted to pH 4.0 with acetic acid 0.1%) as mobile phase. The quantification limit of piplartine was 0.2 μg/mL (0.6 μm ), and the assay was linear up to 5 μg/mL (15.8 μm ), with within‐day and between‐days assay coefficients of variation and relative errors <15%. Piplartine recovery from SC and VS varied from 86 to 96%. The method was suitable to assay samples from skin penetration studies, enabling detection of differences in cutaneous delivery in different skin compartments resulting from treatment with various formulations and time periods. 相似文献
114.
115.
116.
117.
118.
Richard C. Brewster Geňa Hahn Stacey Wynn Lamont Chester Lipka 《Discrete Mathematics》2012,312(10):1638-1645
The reconstruction number of a graph is the smallest number of vertex-deleted subgraphs needed to uniquely determine the graph up to isomorphism. Bollobás showed that almost all graphs have reconstruction number equal to three. McMullen and Radziszowski published a catalogue of all graphs on at most ten vertices with reconstruction number greater than three. We introduce constructions that generalize the examples identified in their work. In particular, we use lexicographic products of vertex transitive graphs with certain starter graphs from the work of Myrvold and from the work of Harary and Plantholt to generate new infinite families of graphs with high reconstruction numbers. In the process, we settle a question of McMullen and Radziszowski. 相似文献
119.
120.