全文获取类型
收费全文 | 1413篇 |
免费 | 51篇 |
出版年
2022年 | 6篇 |
2021年 | 10篇 |
2020年 | 7篇 |
2019年 | 7篇 |
2018年 | 12篇 |
2017年 | 17篇 |
2016年 | 10篇 |
2015年 | 41篇 |
2014年 | 41篇 |
2013年 | 53篇 |
2012年 | 72篇 |
2011年 | 76篇 |
2010年 | 36篇 |
2009年 | 39篇 |
2008年 | 57篇 |
2007年 | 51篇 |
2006年 | 57篇 |
2005年 | 63篇 |
2004年 | 71篇 |
2003年 | 48篇 |
2002年 | 58篇 |
2001年 | 48篇 |
2000年 | 60篇 |
1999年 | 48篇 |
1998年 | 15篇 |
1997年 | 10篇 |
1996年 | 7篇 |
1995年 | 11篇 |
1994年 | 15篇 |
1993年 | 15篇 |
1992年 | 46篇 |
1991年 | 38篇 |
1990年 | 39篇 |
1989年 | 34篇 |
1988年 | 26篇 |
1987年 | 27篇 |
1986年 | 20篇 |
1985年 | 19篇 |
1984年 | 13篇 |
1983年 | 21篇 |
1982年 | 11篇 |
1981年 | 9篇 |
1980年 | 17篇 |
1979年 | 15篇 |
1978年 | 10篇 |
1977年 | 6篇 |
1975年 | 6篇 |
1974年 | 8篇 |
1968年 | 5篇 |
1967年 | 8篇 |
排序方式: 共有1464条查询结果,搜索用时 625 毫秒
91.
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
92.
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
93.
94.
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
95.
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
96.
Morita Y Araki H Sugimoto T Takeuchi K Yamane T Maeda T Yamamoto Y Nishi K Asano M Shirahama-Noda K Nishimura M Uzu T Hara-Nishimura I Koya D Kashiwagi A Ohkubo I 《FEBS letters》2007,581(7):1417-1424
Legumain/asparaginyl endopeptidase (EC 3.4.22.34) is a novel cysteine protease that is abundantly expressed in the late endosomes and lysosomes of renal proximal tubular cells. Recently, emerging evidence has indicated that legumain might play an important role in control of extracellular matrix turnover in various pathological conditions such as tumor growth/metastasis and progression of atherosclerosis. We initially found that purified legumain can directly degrade fibronectin, one of the main components of the extracellular matrix, in vitro. Therefore, we examined the effect of legumain on fibronectin degradation in cultured mouse renal proximal tubular cells. Fibronectin processing can be inhibited by chloroquine, an inhibitor of lysosomal degradation, and can be enhanced by the overexpression of legumain, indicating that fibronectin degradation occurs in the presence of legumain in lysosomes from renal proximal tubular cells. Furthermore, in legumain-deficient mice, unilateral ureteral obstruction (UUO)-induced renal interstitial protein accumulation of fibronectin and renal interstitial fibrosis were markedly enhanced. These findings indicate that legumain might have an important role in extracellular matrix remodeling via the degradation of fibronectin in renal proximal tubular cells. 相似文献
97.
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
98.
1. An apo-NADPH-adreno-ferredoxin reductase (EC 1.18.1.2) was obtained from bovine adrenocortical mitochondria and its physicochemical properties were investigated. 2. The effects of various substances such as NADPH, FAD and adreno-ferredoxin on the interaction of the apo-reductase were investigated by various column chromatographies. 3. The apo- and holo-reductases were found to be separated by adreno-ferredoxin affinity chromatography. 4. The removal of FAD from NADPH-adreno-ferredoxin reductase did not affect the net charge of the reductase. 5. The values of s20,w of apo- and holo-reductases were 3.8 x 10(-13) sec and 3.9 x 10(-13) sec, respectively. 6. The apo-reductase was more easily denatured by heat treatment than the holo-reductase. 7. FAD, and adreno-ferredoxin and both could protect the apo-reductase from thermal inactivation. 相似文献
99.
Ricin toxin A-chain (RTA) is expressed by the castor bean plant and is among the most potent mammalian toxins. Upon activation in the cytosol, RTA depurinates a single adenine from position 4324 of rat 28S ribosomal RNA, causing inactivation of ribosomes by preventing the binding of elongation factors. Kinetic isotope effect studies have established that RTA operates via a D(N)*A(N) mechanism involving an oxacarbenium ion intermediate with bound adenine [Chen, X.-Y., Berti, P. J., and Schramm, V. L. (2000) J. Am. Chem. Soc. 122, 1609-1617]. On the basis of this information, stem-loop RNA molecules were chemically synthesized, incorporating structural features of the oxacarbenium ion-like transition state. A 10-base RNA stem-loop incorporating (1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-1,4-imino-D-ribitol at the depurination site binds four times better (0.57 microM) than the 10-base RNA stem-loop with adenosine at the depurination site (2.2 microM). A 10-base RNA stem-loop with 1,2-dideoxyribitol [(2R,3S)-2-(hydroxymethyl)-3-hydroxytetrahydrofuran] at the depurination site binds with a Kd of 3.2 microM and tightens to 0.75 microM in the presence of 9-deazaadenine. A similar RNA stem-loop with 1,4-dideoxy-1,4-imino-D-ribitol at the depurination site binds with a K(d) of 1.3 microM and improves to 0.65 micro;M with 9-deazaadenine added. When (3S,4R)-4-hydroxy-3-(hydroxymethyl)pyrrolidine was incorporated at the depurination site of a 14-base RNA stem-loop, the Kd was 0.48 microM. Addition of 9-deazaadenine tightens the binding to 0.10 microM whereas added adenine increases the affinity to 12 nM. The results of this study are consistent with the unusual dissociative D(N)*A(N) mechanism determined for RTA. Knowledge of this intermediate has led to the design and synthesis of the highest affinity inhibitor reported for the catalytic site of RTA. 相似文献
100.
Ichikawa K Inagaki T Kachi-Tonai H Kojima Y Nakamura T Nishida H Ueno Y Binding P Gabel CA Lucas V McNiff PA Kojima N 《Biochemical and biophysical research communications》2001,286(4):697-700
LL-Z1271alpha, a fungal metabolite, dose-dependently inhibited interleukin-1beta (IL-1beta) production in lipopolysaccharide (LPS)-stimulated human whole blood. Oral administration of LL-Z1271alpha to LPS-challenged mice caused significant lowering in the IL-1beta levels in peritoneal cavity. Data presented suggest that LL-Z1271alpha inhibits IL-1beta production by a novel mechanism as the inhibitory activity was not due to effects on caspase-1 (IL-1beta converting enzyme), the ATP-induced release mechanism or a lysosomotrophic effect. 相似文献