全文获取类型
收费全文 | 1140篇 |
免费 | 107篇 |
国内免费 | 1篇 |
专业分类
1248篇 |
出版年
2023年 | 7篇 |
2022年 | 16篇 |
2021年 | 26篇 |
2020年 | 15篇 |
2019年 | 21篇 |
2018年 | 21篇 |
2017年 | 15篇 |
2016年 | 34篇 |
2015年 | 31篇 |
2014年 | 45篇 |
2013年 | 64篇 |
2012年 | 71篇 |
2011年 | 62篇 |
2010年 | 52篇 |
2009年 | 43篇 |
2008年 | 62篇 |
2007年 | 47篇 |
2006年 | 62篇 |
2005年 | 43篇 |
2004年 | 61篇 |
2003年 | 45篇 |
2002年 | 33篇 |
2001年 | 40篇 |
2000年 | 26篇 |
1999年 | 20篇 |
1998年 | 18篇 |
1997年 | 11篇 |
1995年 | 5篇 |
1994年 | 5篇 |
1993年 | 9篇 |
1992年 | 13篇 |
1991年 | 15篇 |
1990年 | 23篇 |
1989年 | 17篇 |
1988年 | 16篇 |
1987年 | 16篇 |
1986年 | 13篇 |
1985年 | 11篇 |
1984年 | 10篇 |
1983年 | 6篇 |
1982年 | 10篇 |
1981年 | 6篇 |
1979年 | 9篇 |
1978年 | 5篇 |
1977年 | 11篇 |
1976年 | 8篇 |
1974年 | 6篇 |
1970年 | 6篇 |
1967年 | 5篇 |
1966年 | 4篇 |
排序方式: 共有1248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.
Tapas K. Nandi Hridoy R. Bairagya Bishnu P. Mukhopadhyay K. Sekar Dipankar Sukul Asim K. Bera 《Journal of biosciences》2009,34(1):27-34
The role of invariant water molecules in the activity of plant cysteine protease is ubiquitous in nature. On analysing the
11 different Protein DataBank (PDB) structures of plant thiol proteases, the two invariant water molecules W1 and W2 (W220
and W222 in the template 1PPN structure) were observed to form H-bonds with the Ob atom of Asn 175. Extensive energy minimization and molecular dynamics simulation studies up to 2 ns on all the PDB and solvated
structures clearly revealed the involvement of the H-bonding association of the two water molecules in fixing the orientation
of the asparagine residue of the catalytic triad. From this study, it is suggested that H-bonding of the water molecule at
the W1 invariant site better stabilizes the Asn residue at the active site of the catalytic triad. 相似文献
3.
Piotr Berman Paul Bertone Bhaskar Dasgupta Mark Gerstein Ming-Yang Kao Michael Snyder 《Journal of computational biology》2004,11(4):766-785
In this paper, we consider several variations of the following basic tiling problem: given a sequence of real numbers with two size-bound parameters, we want to find a set of tiles of maximum total weight such that each tiles satisfies the size bounds. A solution to this problem is important to a number of computational biology applications such as selecting genomic DNA fragments for PCR-based amplicon microarrays and performing homology searches with long sequence queries. Our goal is to design efficient algorithms with linear or near-linear time and space in the normal range of parameter values for these problems. For this purpose, we first discuss the solution to a basic online interval maximum problem via a sliding-window approach and show how to use this solution in a nontrivial manner for many of the tiling problems introduced. We also discuss NP-hardness results and approximation algorithms for generalizing our basic tiling problem to higher dimensions. Finally, computational results from applying our tiling algorithms to genomic sequences of five model eukaryotes are reported. 相似文献
4.
Activities of Phosphorylase, glyceraldehyde-3 -phosphate dehydrogenase, lactate dehydrogenase, malate dehydrogenase and succinate
dehydrogenase in the rat endometrial tissue are significantly inhibited by an intrauterine copper device, while it stimulated
glucose-6-phosphate dehydrogenase activity. The copper device decreased the lactate/pyruvate ratio in the tissue; pyruvate
utilizationin vitro by the rat endometrium is also blocked by copper. These findings suggested that the normal carbohydrate metabolism of the
tissue may be affected in presence of copper, thus resulting in a change of the endometrial function, which may be one of
the factors responsible for the contraceptive and pharmacological action of an intrauterine copper device. 相似文献
5.
Detection of Clostridium botulinum Toxin by Local Paralysis Elicited with Intramuscular Challenge 下载免费PDF全文
Clostridium botulinum toxin can be identified by a characteristic, acute local paralysis that follows its injection into the gastrocnemius ("calf" muscle) of mice. The local botulism can be elicited with slightly less than one-tenth the toxin amount that is needed to kill mice by the intraperitoneal (i.p.) challenge route. The practical sensitivities of the intramuscular (i.m.) versus i.p. tests are about equal, however, because maximum sample volume injectable i.m. is 0.1 ml as compared to the 0.5-ml range that can be given i.p. i.m. injection of 10 or more mouse i.p. mean lethal doses causes paralysis in about 1 h, and an i.m. injection of about 0.5 i.p. mean lethal doses causes paralysis in 3 to 4 h. Toxin neutralization by homologous type of antitoxin only can be demonstrated with an incubated mixture of toxin and antitoxin. Although not as convenient as the i.p. method for routine use to detect botulinum toxin, the i.m. method has characteristics which could make it a useful supplement to the presently accepted i.p. procedure. 相似文献
6.
Peroxisome proliferator-activated receptor-gamma agonist 15-deoxy-Delta(12,14)-prostaglandin J(2) ameliorates experimental autoimmune encephalomyelitis 总被引:12,自引:0,他引:12
Diab A Deng C Smith JD Hussain RZ Phanavanh B Lovett-Racke AE Drew PD Racke MK 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(5):2508-2515
Peroxisome proliferator-activated receptors (PPAR) are members of a nuclear hormone receptor superfamily that includes receptors for steroids, retinoids, and thyroid hormone, all of which are known to affect the immune response. Previous studies dealing with PPAR-gamma expression in the immune system have been limited. Recently, PPAR-gamma was identified in monocyte/macrophage cells. In this study we examined the role of PPAR-gamma in experimental autoimmune encephalomyelitis (EAE), an animal model for the human disease multiple sclerosis. The hypothesis we are testing is whether PPAR-gamma plays an important role in EAE pathogenesis and whether PPAR-gamma ligands can inhibit the clinical expression of EAE. Initial studies have shown that the presence of the PPAR-gamma ligand 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ2) inhibits the proliferation of Ag-specific T cells from the spleen of myelin basic protein Ac(1-11) TCR-transgenic mice. 15d-PGJ2 suppressed IFN-gamma, IL-10, and IL-4 production by both Con A- and myelin basic protein Ac(1-11) peptide-stimulated lymphocytes as determined by ELISA and ELISPOT assay. Culture of encephalitogenic T cells with 15d-PGJ2 in the presence of Ag reduced the ability of these cells to adoptively transfer EAE. Examination of the target organ, the CNS, during the course of EAE revealed expression of PPAR-gamma in the spinal cord inflammatory infiltrate. Administration of 15d-PGJ2 before and at the onset of clinical signs of EAE significantly reduced the severity of disease. These results suggest that PPAR-gamma ligands may be a novel therapeutic agent for diseases such as multiple sclerosis. 相似文献
7.
A Basu A Gomes A Gomes S C Dasgupta S C Lahiri 《Indian journal of experimental biology》1990,28(5):451-454
Toxin-L a lethal neuromuscular blocking agent was isolated from the venom of the scorpion, Lychas laevifrons (Pocock), by the CM-cellulose ion-exchange chromatography. It was a homogenous, thermolabile and low molecular weight protein. The toxin produced irreversible blockade of indirect stimulation induced twitch responses on innervated rat phrenic nerve-diaphragm and chick biventer cervicis preparation. The toxin did not produce any contractile response on toad rectus abdominis muscle preparation. On chronically denervated rat diaphragm, the toxin failed to alter the responses induced by direct stimulation, exogenous acetylcholine, potassium chloride and caffeine. Acetylcholine and carbachol induced contractions on isolated chick biventer cervicis remained unaltered by the toxin. Neostigmine failed to alter toxin induced neuromuscular blockade on innervated rat diaphragm. The toxin released a significant amount of acetylcholine from innervated rat diaphragm. It may be concluded that the toxin acts presynaptically through the release of acetylcholine, thereby producing neuromuscular blockade. 相似文献
8.
Response of microbial populations to environmental disturbance 总被引:18,自引:0,他引:18
Taxonomic and genetic diversities of microbial communities disturbed by chemical pollutants were lower than in undisturbed
reference communities. The dominant populations within the disturbed communities had enhanced physiological tolerances and
substrate utilization capabilities, indicating that generalized physiological versatility is an adaptive characteristic of
populations that successfully compete within disturbed communities. 相似文献
9.
Yeast cells are incapable of translating RNAs containing the poliovirus 5'' untranslated region: evidence for a translational inhibitor. 下载免费PDF全文
We have expressed in the yeast Saccharomyces cerevisiae a full-length poliovirus cDNA clone under the control of the GAL10 promoter to better characterize the effect of poliovirus on host cell metabolism. We find that yeast cells are unable to translate poliovirus RNA in vivo and that this inhibition is mediated through the 5' untranslated region of the viral RNA. The in vivo inhibition of translation of poliovirus RNA and P2CAT RNA (which contains the 5' untranslated region fused upstream of the bacterial chloramphenicol transferase gene) can be mimicked in vitro in yeast translation lysates. In fact, a trans-acting inhibitor present in yeast lysates can inhibit translation of either poliovirus or P2CAT RNA in HeLa cell translation lysates. In contrast, when the inhibitor is added to translations programmed with chloramphenicol acetyltransferase RNA, yeast prepro-alpha-factor RNA, or an RNA containing the internal ribosome entry site of encephalomyocarditis virus, no inhibition is seen. The inhibitory activity has been partially purified by DEAE-Sephacel chromatography. The partially purified inhibitor is heat stable, escapes phenol extraction, is resistant to proteinase K and DNase I treatment, and is sensitive to RNase A digestion, suggesting that the inhibitor is an RNA. In an in vitro translation assay, the inhibitory activity can be overcome by increasing the concentration of HeLa cell lysate but not P2CAT RNA, suggesting that the inhibitor interacts (directly or indirectly) with one or more components of the HeLa cell translational machinery rather than with the viral RNA. 相似文献
10.
LeBron C Pal P Brait M Dasgupta S Guerrero-Preston R Looijenga LH Kowalski J Netto G Hoque MO 《Genomics》2011,97(6):341-349
Testicular germ cell tumors (TGCT) represent the most common malignancy among young males. To our knowledge no comprehensive Copy Number Variation (CNVs) studies of TGCT using high-resolution Single Nucleotide Polymorphism (SNP) array have been performed. By a genome-wide analysis of CNV and loss of heterozygosity (LOH) in 25 primary seminomas, we confirmed several previously reported genomic alterations and discovered eight novel genomic alterations including amplifications and homozygous deletions. Moreover, a comparison of genomic alterations of early and late stage seminoma identified CNVs that correlate with progression, which included deletions in chromosomes 4q, 5p, 9q, 13q and 20p and amplifications in chromosomes 9q and 13q. We compared previously perform Affymetrix expression analysis in a subset of samples and found robust correlation between expression and genomic alterations. Furthermore, high correlations (40-75%) were observed between CNV by SNP analysis and quantitative PCR. Our findings may lead to better understanding of TGTC's pathogenesis. 相似文献