全文获取类型
收费全文 | 980篇 |
免费 | 79篇 |
专业分类
1059篇 |
出版年
2022年 | 13篇 |
2021年 | 18篇 |
2020年 | 8篇 |
2019年 | 10篇 |
2018年 | 16篇 |
2017年 | 8篇 |
2016年 | 15篇 |
2015年 | 43篇 |
2014年 | 34篇 |
2013年 | 60篇 |
2012年 | 49篇 |
2011年 | 60篇 |
2010年 | 31篇 |
2009年 | 35篇 |
2008年 | 46篇 |
2007年 | 42篇 |
2006年 | 42篇 |
2005年 | 39篇 |
2004年 | 39篇 |
2003年 | 51篇 |
2002年 | 26篇 |
2001年 | 29篇 |
2000年 | 34篇 |
1999年 | 30篇 |
1998年 | 10篇 |
1997年 | 6篇 |
1996年 | 9篇 |
1995年 | 6篇 |
1994年 | 9篇 |
1992年 | 29篇 |
1991年 | 11篇 |
1990年 | 24篇 |
1989年 | 17篇 |
1988年 | 15篇 |
1987年 | 17篇 |
1986年 | 15篇 |
1985年 | 12篇 |
1984年 | 11篇 |
1983年 | 6篇 |
1982年 | 7篇 |
1981年 | 5篇 |
1980年 | 11篇 |
1979年 | 6篇 |
1978年 | 9篇 |
1977年 | 5篇 |
1976年 | 9篇 |
1975年 | 3篇 |
1974年 | 4篇 |
1973年 | 7篇 |
1972年 | 3篇 |
排序方式: 共有1059条查询结果,搜索用时 15 毫秒
1.
S Ravichandran J Dasgupta C Chakrabarti S Ghosh M Singh J K Dattagupta 《Protein engineering》2001,14(5):349-357
A double-headed chymotrypsin inhibitor, WCI, from winged bean seeds was cloned for structural and biochemical studies. The inhibitor was subjected to two point mutations at a conserved position, Asn14. This residue, known to have a pivotal role in stabilizing the first reactive-site loop (Gln63-Phe68) of the inhibitor, is highly conserved in the sequences of the other members of Kunitz (STI) family as well as in the sequences of Kazal family of serine protease inhibitors. The mutants, N14K and N14D, were subjected to biochemical assay and their characteristics were compared with those of the recombinant inhibitor (rWCI). Crystallographic studies of the recombinant and the mutant proteins are discussed. These studies were primarily aimed at understanding the importance of the protein scaffolding towards the conformational rigidity of the reactive-site loop. Our analysis reveals that, as the Lys14 side chain takes an unusual fold in N14K and the Asp14 side chain in N14D interacts with the loop residues by water-mediated hydrogen bonds, the canonical conformation of the loop has remained effectively intact in both the mutant structures. However, minor alterations such as a 2-fold increase in the inhibitory affinity towards the cognate enzyme were observed. 相似文献
2.
A composite plot for depicting in two dimensions the conformation and the secondary structural features of protein residues has been developed. Instead of presenting the exact values of the main- and side-chain torsion angles (φ, psi and chi(1)), it indicates the region in the three-dimensional conformational space to which a residue belongs. Other structural aspects, like the presence of a cis peptide bond and disulfide linkages, are also displayed. The plot may be used to recognize patterns in the backbone and side-chain conformation along a polypeptide chain and to compare protein structures derived from X-ray crystallography, NMR spectroscopy or molecular modelling studies and also to highlight the effect of mutation on structure. 相似文献
3.
4.
5.
Two types of phospholipid vesicles capable of mutual recognition have been tailor-made to serve as a model system for the study of carbohydrate-mediated cellular adhesion. One of the vesicles contained a fatty acid conjugate of a galactose specific lectin (lectin vesicle) and the other an asialoganglioside with a reactive terminal galactose residue (galactose vesicle). The kinetics of aggregation of these two types of vesicles was followed by monitoring time-dependent change in turbidity. A 10-100-fold enhancement in the forward rate constant (kf ranging from 7.1 x 10(5) to 4.5 x 10(7) M-1.s-1 at 27 degrees C) was observed when compared with that for the lectin-galactose system in solution (kf being 4.5 x 10(5) M-1.s-1), reported in the literature. A study of the influence of vesicle size on the rate of aggregation showed that enhancement depended on the curvature of the galactose vesicle rather than the density of asialoganglioside suggesting a possible diffusion in the plane of the membrane. The ratio, kf/kd is found to be approx. 10(10) M-1 indicating that the formation of multiple bonds plays a role for stable adhesion. 相似文献
6.
Chronic myelogenous leukemia (CML) is a hematologic malignancy characterized by excessive growth of myeloid cells and their progenitors. The proportion of spectrin dimers compared to tetramers extracted from membranes at 4 degrees C, under low ionic strength conditions, increased in CML erythrocytes. These also displayed abnormal thermal sensitivity (between 45 and 46 instead of 49 degrees C). Crosslinking with the bifunctional reagent, dimethyl adipimidate (8.6 A) showed significant organizational modification of not only spectrin, but other cytoskeletal components such as ankyrin, bands 4.2 and 5. Enhanced concanavalin A (Con-A) agglutinability of CML erythrocytes also suggests altered topographic distribution of a functionally important membrane protein, band 3. The anion transport activities of erythrocytes from patients with CML and normal donors were comparable. In CML erythrocytes, significant reduction in the number of ankyrin-binding sites, present in the cytoplasmic domain of band 3, may lead to partial loss of cytoskeletal anchorage to the bilayer and account for their increased Con-A agglutinability and heat sensitivity and may lead to their premature removal from the circulation. 相似文献
7.
Induction of 6-thioguanine (TG) resistance by chemical mutagens was examined in a line of cells derived from a human epithelial teratocarcinoma cell clone. The cells, designated as P3 cells, have a stable diploid karyotype with 46(XX) chromosomes, including a translocation between chromosomes 15 and 20. Efficient recovery of TG-resistant mutants induced by the direct-acting mutagens: N-methyl-N'-nitro-N-nitrosoguanidine (MNNG); 7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10 -tetrahydrobenzo[a]pyrene (BPDE); and benzo[a]pyrene (B[a]P); activated in a cell-mediated assay, required an expression time of 7 days and a saturation density of 2 X 10(4) cells/60-mm petri dish. The TG-resistant mutant cells induced by MNNG and BPDE maintained their resistant phenotype 4-6 weeks after isolation. This mutant phenotype was associated with a more than 10-fold reduction in hypoxanthine-guanine phosphoribosyl transferase (HGPRT) activity relative to that of the parental P3 cell line, which was shown to catalyze the formation of 4.6 pmoles inosine-5'-monophosphate (IMP)/min/microgram protein. Induction of TG resistance was also observed in P3 cells cocultivated in a cell-mediated assay with human breast carcinoma cells, which are capable of polycyclic aromatic hydrocarbon (PAH) metabolism, after treatment with the carcinogenic PAHs: B[a]P, chrysene, 7,12-dimethylbenz[a]anthracene (DMBA), and 3-methylcholanthrene (MCA). The degree of mutant induction in this assay was related to the carcinogenic potency of these PAHs in experimental animals. The most potent mutagen was DMBA, followed in decreasing order by MCA, B[a]P, and chrysene. DMBA, at 0.4 microM, increased the frequency of mutants for TG resistance from 2 for the control to about 200 TG-resistant mutants/10(6) colony-forming cells (CFC). Benzo[e]pyrene (B[e]P) and pyrene, which are not carcinogenic, were not effective in the assay. None of the PAHs was mutagenic in the P3 cells cultivated in the absence of the PAH-metabolizing cells. These results indicate that the P3 cells can be useful for the study of mutagenesis at the HGPRT locus by direct-acting chemical mutagens, as well as by chemicals activated in a cell-mediated assay. 相似文献
8.
By SDS-PAGE or gel filtration on Sephadex G-25, lipopolysaccharide (LPS) isolated from Vibrio cholerae 569B (Inaba) can be separated into two distinct fractions, one corresponding to smooth LPS and the other to rough LPS. Pulse-labelling of LPS with [14C]glucose showed that the rough form is synthesized first followed by the biosynthesis of the smooth form. A preferential release of the smooth LPS of V. cholerae 569B was also detected during normal growth of cells. 相似文献
9.
Shyamali Mukherjee Mihir Nag Tultul Nayyar Indrani Maitra Parul Chakrabarti Pramod R. Dasgupta 《Journal of biosciences》1986,10(3):311-317
The effect of estradiol-17β and progesterone given separately as well as in combination on the rate of hydrogen peroxide formation
and lipid peroxidation in the uteri of ovariectomized rats was studied. Estradiol in 3μg dose per day per animal elicited maximum stimulatory response and progesterone (100μg), on the other hand, was without any such effect. However, progesterone given along with estradiol completely prevented the
effect due to the latter. In the same way, vitamin E, a well known antioxidant was found to be extremelv effective in protecting
the uterus from the highly peroxidative action of estradiol-17β. 相似文献
10.