全文获取类型
收费全文 | 4364篇 |
免费 | 427篇 |
国内免费 | 2篇 |
出版年
2023年 | 18篇 |
2022年 | 44篇 |
2021年 | 81篇 |
2020年 | 43篇 |
2019年 | 43篇 |
2018年 | 67篇 |
2017年 | 73篇 |
2016年 | 127篇 |
2015年 | 204篇 |
2014年 | 219篇 |
2013年 | 260篇 |
2012年 | 337篇 |
2011年 | 280篇 |
2010年 | 211篇 |
2009年 | 181篇 |
2008年 | 255篇 |
2007年 | 230篇 |
2006年 | 228篇 |
2005年 | 238篇 |
2004年 | 234篇 |
2003年 | 204篇 |
2002年 | 177篇 |
2001年 | 73篇 |
2000年 | 64篇 |
1999年 | 55篇 |
1998年 | 44篇 |
1997年 | 31篇 |
1996年 | 29篇 |
1995年 | 36篇 |
1994年 | 23篇 |
1993年 | 31篇 |
1992年 | 33篇 |
1991年 | 37篇 |
1990年 | 27篇 |
1989年 | 36篇 |
1988年 | 45篇 |
1987年 | 26篇 |
1986年 | 32篇 |
1985年 | 24篇 |
1984年 | 23篇 |
1982年 | 22篇 |
1981年 | 15篇 |
1979年 | 25篇 |
1978年 | 14篇 |
1977年 | 14篇 |
1976年 | 16篇 |
1974年 | 14篇 |
1973年 | 15篇 |
1970年 | 19篇 |
1969年 | 15篇 |
排序方式: 共有4793条查询结果,搜索用时 943 毫秒
981.
John A. Hickman Owen C. Blair Anita L. Stepanowski Alan C. Sartorelli 《生物化学与生物物理学报:生物膜》1984,778(3):457-462
Ionophore-induced changes in the cell-associated fluorescence of samples of approx. 50 000 individual murine L1210 leukemia cells which had been incubated with the voltage-sensitive dye 3,3′-dihexyloctacarbocyanine iodide (DiOC6(3)) were monitored by flow cytometry. The K+ ionophore valinomycin (1 μM) produced homogeneous changes in the fluorescence of the entire population, the magnitude of which was dependent upon the concentration of extracellular K+. These changes allowed the estimation of the potassium equilibrium potential of the cells, by the null-point method, to be – 11.9 mV. The Ca2+ ionophore A23187 (500 nM) produced heterogeneous changes in fluorescence, with populations of both hyperpolarised and depolarised cells. In addition, the depolarised population underwent an apparent size change, with a reduction in cell volume. This heterogeneity of response resulted in a minimal change in the median fluorescence value for the whole population, which suggests that it would not have been detectable by methods dependent upon net population-averaged changes in fluorescence. Removal of extracellular Na+ or preincubation of cells with amiloride (500 μM) effectively eliminated the depolarised population. Removal of extracellular K+ increased the hyperpolarised population. These findings provide evidence for the presence of Ca2+-induced Na+ exchange and Ca2+-induced K+ efflux mechanisms in these cells which may be expressed simultaneously in the cell population. 相似文献
982.
Purification of (1→3)-β-glucan endohydrolase isoenzyme II from germinated barley and determination of its primary structure from a cDNA clone 总被引:2,自引:0,他引:2
Peter B. Høj Dallas J. Hartman Nick A. Morrice Danny N. P. Doan Geoffrey B. Fincher 《Plant molecular biology》1989,13(1):31-42
A (13)--D-glucan 3-glucanonydrolase (EC 3.2.1.39) of apparent M
r 32 000, designated GII, has been purified from germinated barley grain and characterized. The isoenzyme is resolved from a previously purified isoenzyme (GI) on the basis of differences in their isoelectric points; (13)--glucanases GI and GII have pI values of 8.6 and 10.0, respectively. Comparison of the sequences of their 40 NH2-terminal amino acids reveals 68% positional identity. A 1265 nucleotide pair cDNA encoding (13)--glucanase isoenzyme GII has been isolated from a library prepared with mRNA of 2-day germinated barley scutella. Nucleotide sequence analysis of the cDNA has enabled the complete primary structure of the 306 amino acid (13)--glucanase to be deduced, together with that of a putative NH2-terminal signal peptide of 28 amino acid residues. The (13)--glucanase cDNA is characterized by a high (G+C) content, which reflects a strong bias for the use of G or C in the wobble base position of codons. The amino acid sequence of the (13)--glucanase shows highly conserved internal domains and 52% overall positional identity with barley (13, 14)--glucanase isoenzyme EII, an enzyme of related but quite distinct substrate specificity. Thus, the (13)--glucanases, which may provide a degree of protection against microbial invasion of germinated barley grain through their ability to degrade fungal cell wall polysaccharides, appear to share a common evolutionary origin with the (13, 14)--glucanases, which function to depolymerize endosperm cell walls in the germinated grain. 相似文献
983.
Y Ogiso L Gutierrez L S Wrathall Y Y Lu D G Blair D J Clanton Y W Hwang T Y Shih 《Cell growth & differentiation》1990,1(5):217-224
Site-directed mutagenesis of the conserved sequence motifs of p21 generated a group of mutant p21s defective in GTP binding. Some of these mutants were highly transforming, whereas others were transformation defective. Among the latter group, we found two mutants, derived from the v-H-ras oncogene by substituting the asparagine-116 with tyrosine and isoleucine, that exhibited a trans-dominant activity of suppressing the transformed phenotype of NIH3T3 cells induced by a long terminal repeat-linked c-H-ras and a wild-type v-H-ras. They caused reduction of the colony-forming efficiency in soft agar (78% in c-ras-transformed cells; 55% in v-ras cells) and morphological reversion of ras transformants. Subclones of revertants expressed a great excess of mutant p21 relative to the c-ras p21 present in these cells. These mutants were not lethal to NIH3T3 cells. Apparently, defective proteins encoded by suppressor mutants sequestered vital targets for ras function. Suppressor mutants also induced morphological reversion of NIH3T3 cells transformed by src, fes/flp, sis, and fms oncogenes, suggesting that these oncogenes function upstream to ras in the signaling pathways. Cells transformed by mos and a chemical carcinogen were unaffected. 相似文献
984.
W H Schaefer B Kakkad J A Crow I A Blair D E Ong 《The Journal of biological chemistry》1989,264(7):4212-4221
Cellular retinol-binding protein type II (CRBP(II)) is a major protein in the small intestine, accounting for more than 1% of the soluble protein recovered from rat jejunal mucosa. Two forms of the protein, called CRBP(II)A and CRBP(II)B, were purified from rat small intestine using a three-column procedure. The two forms were present in equal abundance. The primary structures of CRBP(II)A and CRBP(II)B were determined using a combination of techniques including amino acid composition and sequence analyses, and fast atom bombardment and gas chromatography-electron impact mass spectrometry. The primary structures of both proteins were found to be identical, but they differed in their NH2-terminal processing. CRBP(II)B was acetylated at its NH2 terminus, while CRBP(II)A was not. The results also confirmed the amino acid sequence of CRBP(II)A that was deduced from the cDNA sequence by Li et al. (Li, E., Demmer, L. A., Sweetser, D. A., Ong, D. E., and Gordon, J. I. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 5770-5783). Antibodies capable of distinguishing between the two forms of CRBP(II) were used for immunohistochemical studies which indicated that the organ and cellular distributions of the two forms were identical. The 50% acetylation observed here in vivo fits the pattern predicted by recent in vitro studies which described the effect of NH2-terminal sequence on cotranslational NH2-terminal processing of cytosolic proteins (Boissel, J. P., Kasper, T. J., and Bunn, H. F. (1988) J. Biol. Chem. 263, 8443-8449). Our results provide a basis for investigating the possibility of different roles of CRBP(II)A and CRBP(II)B within cells, as well as the importance of acetylation of the amino terminus for these biological functions. 相似文献
985.
986.
R. Blair Gould 《BMJ (Clinical research ed.)》1935,2(3901):701-702
987.
Nick Wierckx Frank Koopman Luaine Bandounas Johannes H. De Winde Harald J. Ruijssenaars 《Microbial biotechnology》2010,3(3):336-343
The formation of toxic fermentation inhibitors such as furfural and 5-hydroxy-2-methylfurfural (HMF) during acid (pre-)treatment of lignocellulose, calls for the efficient removal of these compounds. Lignocellulosic hydrolysates can be efficiently detoxified biologically with microorganisms that specifically metabolize the fermentation inhibitors while preserving the sugars for subsequent use by the fermentation host. The bacterium Cupriavidus basilensis HMF14 was isolated from enrichment cultures with HMF as the sole carbon source and was found to metabolize many of the toxic constituents of lignocellulosic hydrolysate including furfural, HMF, acetate, formate and a host of aromatic compounds. Remarkably, this microorganism does not grow on the most abundant sugars in lignocellulosic hydrolysates: glucose, xylose and arabinose. In addition, C. basilensis HMF14 can produce polyhydroxyalkanoates. Cultivation of C. basilensis HMF14 on wheat straw hydrolysate resulted in the complete removal of furfural, HMF, acetate and formate, leaving the sugar fraction intact. This unique substrate profile makes C. basilensis HMF14 extremely well suited for biological removal of inhibitors from lignocellulosic hydrolysates prior to their use as fermentation feedstock. 相似文献
988.
Neil Garton Nick Bailey Mark Bamford Emmanuel Demont Irene Farre-Gutierrez Gail Hutley Gianpaolo Bravi Paula Pickering 《Bioorganic & medicinal chemistry letters》2010,20(3):1049-1054
We report the identification of a novel biaryl template for H+/K+ ATPase inhibition. Evaluation of critical SAR features within the biaryl imidazole framework and the use of pharmacophore modelling against known imidazopyridine and azaindole templates suggested that the geometry of the molecule is key to achieving activity. Herein we present our work optimising the potency of the molecule through modifications and substitutions to each of the ring systems. In particular sub-micromolar potency is achieved with (4b) presumably through a proposed intramolecular hydrogen bond that ensures the required imidazole basic centre is appropriately located. 相似文献
989.
Ian T. Crosby David G. Bourke Eric D. Jones Paula J. de Bruyn David Rhodes Nick Vandegraaff Susan Cox Jonathan A.V. Coates Alan D. Robertson 《Bioorganic & medicinal chemistry》2010,18(17):6442-6450
The synthesis of a new series of conocurvone analogues is presented that explores the importance of the pyran rings of conocurvone, their degree of unsaturation as well as the role of alkoxy functionalities as pyran ring replacements, for the inhibition of the HIV-1 integrase (IN) enzyme. Difficulties in synthesising a trimeric naphthoquinone where the central quinone bears a peri-dihydropyran ring was attributed to distortion of the electrophilic dihaloquinone successfully utilised in the past. Increased electron density could also be a factor in reducing reactivity. The desired central dihydropyran bearing trimeric naphthoquinone was successfully synthesised by using a more reactive bromo-tosyloxyquinone intermediate. A maleimide derivative, where the central quinone between the pendant hydroxyquinones was replaced, was successfully synthesised and although it exhibited comparable enzyme inhibitory activity it had negligible HIV inhibitory cellular activity. Compounds were assessed for activity in both in vitro assays using purified recombinant HIV-1 IN and demonstrated superior or comparable activity to conocurvone derivatives previously reported. 相似文献
990.