全文获取类型
收费全文 | 1319篇 |
免费 | 49篇 |
出版年
2021年 | 8篇 |
2019年 | 6篇 |
2018年 | 7篇 |
2017年 | 15篇 |
2016年 | 10篇 |
2015年 | 32篇 |
2014年 | 31篇 |
2013年 | 37篇 |
2012年 | 61篇 |
2011年 | 74篇 |
2010年 | 33篇 |
2009年 | 32篇 |
2008年 | 55篇 |
2007年 | 41篇 |
2006年 | 59篇 |
2005年 | 55篇 |
2004年 | 64篇 |
2003年 | 46篇 |
2002年 | 58篇 |
2001年 | 48篇 |
2000年 | 61篇 |
1999年 | 47篇 |
1998年 | 15篇 |
1997年 | 9篇 |
1996年 | 8篇 |
1995年 | 11篇 |
1994年 | 18篇 |
1993年 | 14篇 |
1992年 | 48篇 |
1991年 | 36篇 |
1990年 | 40篇 |
1989年 | 34篇 |
1988年 | 26篇 |
1987年 | 26篇 |
1986年 | 20篇 |
1985年 | 19篇 |
1984年 | 13篇 |
1983年 | 19篇 |
1982年 | 12篇 |
1981年 | 11篇 |
1980年 | 15篇 |
1979年 | 16篇 |
1978年 | 11篇 |
1977年 | 7篇 |
1975年 | 6篇 |
1974年 | 8篇 |
1971年 | 6篇 |
1970年 | 5篇 |
1968年 | 5篇 |
1967年 | 8篇 |
排序方式: 共有1368条查询结果,搜索用时 187 毫秒
91.
Zhe Nie Victoria Feher Srinivasa Natala Christopher McBride Andre Kiryanov Benjamin Jones Betty Lam Yan Liu Stephen Kaldor Jeffrey Stafford Kouki Hikami Noriko Uchiyama Tomohiro Kawamoto Yuichi Hikichi Shin-ichi Matsumoto Nobuyuki Amano Lilly Zhang David Hosfield Takashi Ichikawa 《Bioorganic & medicinal chemistry letters》2013,23(12):3662-3666
Using structure-based drug design, we identified and optimized a novel series of pyrimidodiazepinone PLK1 inhibitors resulting in the selection of the development candidate TAK-960. TAK-960 is currently undergoing Phase I evaluation in adult patients with advanced solid malignancies. 相似文献
92.
Hirotaka Kashiwagi Yoshiyuki Ono Masateru Ohta Susumu Itoh Fumihiko Ichikawa Suguru Harada Satoshi Takeda Nobuo Sekiguchi Masaki Ishigai Tadakatsu Takahashi 《Bioorganic & medicinal chemistry》2013,21(7):1823-1833
In an extension of our study on gamma hydroxy carboxylic acid analogs, we explored a series of nonsecosteroidal vitamin D receptor (VDR) agonists in which 1,3-diol of 1,25(OH)2D3 had been replaced by aryl acetic acid. These analogs showed very potent activity in vitro compared with 1,25(OH)2D3. An X-ray analysis of 8d showed that the inserted phenyl ring well mimicked the folded methylene linker of the gamma hydroxy carboxylic acid moiety but the carboxylic acid of 8d interacted with VDR in a different manner from gamma hydroxy carboxylic acids. Through our in vivo screening in an osteoporosis rat model using immature rats, we identified a potent active vitamin D3 analog, compound 7e. In mature rats of the same model, compound 7e also showed good PK profiling and excellent ability to prevent bone mineral density loss without severe hypercalcemia. Our nonsecosteroidal VDR agonist 7e (CH5036249) could be a possible new drug candidate for treating osteoporosis in human. 相似文献
93.
94.
Maiko Matsushita Yohei Otsuka Naoya Tsutsumida Chiaki Tanaka Akane Uchiumi Koji Ozawa Takuma Suzuki Daiju Ichikawa Hiroyuki Aburatani Shinichiro Okamoto Yutaka Kawakami Yutaka Hattori 《PloS one》2016,11(1)
The homeobox protein, PEPP2 (RHOXF2), has been suggested as a cancer/testis (CT) antigen based on its expression pattern. However, the peptide epitope of PEPP2 that is recognized by cytotoxic T cells (CTLs) is unknown. In this study, we revealed that PEPP2 gene was highly expressed in myeloid leukemia cells and some other hematological malignancies. This gene was also expressed in leukemic stem-like cells. We next identified the first reported epitope peptide (PEPP2271-279). The CTLs induced by PEPP2271-279 recognized PEPP2-positive target cells in an HLA-A*24:02-restricted manner. We also found that a demethylating agent, 5-aza-2’-deoxycytidine, could enhance PEPP2 expression in leukemia cells but not in blood mononuclear cells from healthy donors. The cytotoxic activity of anti-PEPP2 CTL against leukemic cells treated with 5-aza-2’-deoxycytidine was higher than that directed against untreated cells. These results suggest a clinical rationale that combined treatment with this novel antigen-specific immunotherapy together with demethylating agents might be effective in therapy-resistant myeloid leukemia patients. 相似文献
95.
96.
Kazuki Yamamoto Akira Katsuyama Satoshi Ichikawa 《Bioorganic & medicinal chemistry》2019,27(8):1714-1719
Elucidating a structure-activity relationship study by evaluating a series of truncated analogues is a simple but important and effective tactic in medicinal chemistry based on natural products with a large and complex chemical structure. In this study, a series of truncated analogues of tunicamycin V were designed and synthesized and their MraY inhibitory activity was investigated in order to gain insight into the effect of these moieties on MraY inhibition. 相似文献
97.
Yu Kitadate David J. Jörg Moe Tokue Ayumi Maruyama Rie Ichikawa Soken Tsuchiya Eri Segi-Nishida Toshinori Nakagawa Aya Uchida Chiharu Kimura-Yoshida Seiya Mizuno Fumihiro Sugiyama Takuya Azami Masatsugu Ema Chiyo Noda Satoru Kobayashi Isao Matsuo Yoshiakira Kanai Shosei Yoshida 《Cell Stem Cell》2019,24(1):79-92.e6
98.
A unique multibranched cyclomaltooligosaccharide (cyclodextrin, CD) of 6(1),6(3),6(5)-tri-O-alpha-maltosyl-cyclomaltoheptaose [6(1),6(3),6(5)-tri-O-alpha-maltosyl-beta-cyclodextrin, (G(2))(3)-betaCD] was prepared. The physicochemical and biological properties of (G(2))(3)-betaCD were determined together with those of monobranched CDs (6-O-alpha-D-glucopyranosyl-alpha-cyclodextrin (G(1)-alphaCD), 6-O-alpha-D-glucopyranosyl-beta-cyclodextrin (G(1)-betaCD), and 6-O-alpha-maltosyl-beta-cyclodextrin (G(2)-betaCD)). NMR spectra of (G(2))(3)-betaCD were measured using various 2D NMR techniques. The solubility of (G(2))(3)-betaCD in water and MeOH-water solutions was extremely high in comparison with nonbranched betaCD and was about the same as that of the other monobranched betaCDs. The formation of an inclusion complex of (G(2))(3)-betaCD with stereoisomers (estradiol, retinoic acid, quinine, citral, and glycyrrhetinic acid) depends on the cis-trans isomers of guest compounds. The cis isomers of estradiol, retinoic acid, and glycyrrhetinic acid were included more than their trans isomers, while the trans isomers of citral and quinine fit more tightly than their cis isomers. (G(2))(3)-betaCD was the most effective host compound in the cis-trans resolution of glycyrrhetinic acid. Among the branched betaCDs, (G(2))(3)-betaCD exhibited the weakest hemolytic activity in human erythrocytes and showed negligible cytotoxicity in Caco-2 cells up to 200 microM. These results indicate unique characteristics of (G(2))(3)-betaCD in some biological responses of cultured cells. 相似文献
99.
Ichikawa H No H Takei S Takashimizu I Yue F Cui L Ogiwara N Johkura K Nishimoto Y Sasaki K 《Cryobiology》2007,54(3):290-293
Cryopreservation of embryonic stem (ES) cells is essential to establish them as a resource for regenerative therapy. We evaluated survival adhesion rate, cell structure, gene expression, and multipotency of frozen and thawed embryoid bodies (EBs) derived from mouse ES cells. EBs were cryopreserved using the BICELL and the Program Freezer. After one week the EBs were thawed and cultured. EBs prepared in the Program Freezer had the highest survival adhesion (Program Freezer; 55-69%, BICELL; 30-38%). Though many cells in the thawed EBs were damaged, some were not, especially those prepared in the Program Freezer. RT-PCR analysis showed that genes characteristic of the three embryonic germ layers were expressed in thawed EBs cultured for one week. EBs transplanted into mice formed teratomas consisting of cells derived from the three germ layers. In conclusion, EBs frozen in the Program Freezer had higher survival adhesion rates compared to the BICELL and formed differentiated cells characteristic of the three embryonic germ layers. 相似文献
100.
Lieberman Joshua A. Fiorito Joseph Ichikawa Doug Fang Ferric C. Rakita Robert M. Bourassa Lori 《Mycopathologia》2019,184(5):671-676
Mycopathologia - Medicopsis species are rare fungal pathogens that frequently resist common antifungal therapies and are difficult to identify morphologically as conidia are produced in pycnidia, a... 相似文献