全文获取类型
收费全文 | 39331篇 |
免费 | 3128篇 |
国内免费 | 124篇 |
出版年
2022年 | 386篇 |
2021年 | 773篇 |
2020年 | 506篇 |
2019年 | 698篇 |
2018年 | 824篇 |
2017年 | 717篇 |
2016年 | 1059篇 |
2015年 | 1620篇 |
2014年 | 1702篇 |
2013年 | 2218篇 |
2012年 | 2434篇 |
2011年 | 2298篇 |
2010年 | 1582篇 |
2009年 | 1292篇 |
2008年 | 1837篇 |
2007年 | 1729篇 |
2006年 | 1648篇 |
2005年 | 1426篇 |
2004年 | 1429篇 |
2003年 | 1334篇 |
2002年 | 1342篇 |
2001年 | 1144篇 |
2000年 | 992篇 |
1999年 | 898篇 |
1998年 | 443篇 |
1997年 | 431篇 |
1996年 | 328篇 |
1995年 | 330篇 |
1994年 | 263篇 |
1993年 | 319篇 |
1992年 | 581篇 |
1991年 | 549篇 |
1990年 | 516篇 |
1989年 | 457篇 |
1988年 | 376篇 |
1987年 | 368篇 |
1986年 | 343篇 |
1985年 | 397篇 |
1984年 | 362篇 |
1983年 | 326篇 |
1982年 | 236篇 |
1981年 | 246篇 |
1980年 | 222篇 |
1979年 | 291篇 |
1978年 | 254篇 |
1977年 | 277篇 |
1976年 | 261篇 |
1975年 | 257篇 |
1974年 | 259篇 |
1973年 | 240篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
91.
Duccio Malinverni Simone Marsili Alessandro Barducci Paolo De Los Rios 《PLoS computational biology》2015,11(6)
Hsp70s are a class of ubiquitous and highly conserved molecular chaperones playing a central role in the regulation of proteostasis in the cell. Hsp70s assist a myriad of cellular processes by binding unfolded or misfolded substrates during a complex biochemical cycle involving large-scale structural rearrangements. Here we show that an analysis of coevolution at the residue level fully captures the characteristic large-scale conformational transitions of this protein family, and predicts an evolutionary conserved–and thus functional–homo-dimeric arrangement. Furthermore, we highlight that the features encoding the Hsp70 dimer are more conserved in bacterial than in eukaryotic sequences, suggesting that the known Hsp70/Hsp110 hetero-dimer is a eukaryotic specialization built on a pre-existing template. 相似文献
92.
During lung development, Fibroblast growth factor 10 (Fgf10), which is expressed in the distal mesenchyme and regulated by Wnt signaling, acts on the distal epithelial progenitors to maintain them and prevent them from differentiating into proximal (airway) epithelial cells. Fgf10-expressing cells in the distal mesenchyme are progenitors for parabronchial smooth muscle cells (PSMCs). After naphthalene, ozone or bleomycin-induced airway epithelial injury, surviving epithelial cells secrete Wnt7b which then activates the PSMC niche to induce Fgf10 expression. This Fgf10 secreted by the niche then acts on a subset of Clara stem cells to break quiescence, induce proliferation and initiate epithelial repair. Here we show that conditional deletion of the Wnt target gene c-Myc from the lung mesenchyme during development does not affect proper epithelial or mesenchymal differentiation. However, in the adult lung we show that after naphthalene-mediated airway epithelial injury c-Myc is important for the activation of the PSMC niche and as such induces proliferation and Fgf10 expression in PSMCs. Our data indicate that conditional deletion of c-Myc from PSMCs inhibits airway epithelial repair, whereas c-Myc ablation from Clara cells has no effect on airway epithelial regeneration. These findings may have important implications for understanding the misregulation of lung repair in asthma and COPD. 相似文献
93.
The plant-specific insert is an approximately 100-residue domain found exclusively within the C-terminal lobe of some plant aspartic proteases. Structurally, this domain is a member of the saposin-like protein family, and is involved in plant pathogen defense as well as vacuolar targeting of the parent protease molecule. Similar to other members of the saposin-like protein family, most notably saposins A and C, the recently resolved crystal structure of potato (Solanum tuberosum) plant-specific insert has been shown to exist in a substrate-bound open conformation in which the plant-specific insert oligomerizes to form homodimers. In addition to the open structure, a closed conformation also exists having the classic saposin fold of the saposin-like protein family as observed in the crystal structure of barley (Hordeum vulgare L.) plant-specific insert. In the present study, the mechanisms of tertiary and quaternary conformation changes of potato plant-specific insert were investigated in silico as a function of pH. Umbrella sampling and determination of the free energy change of dissociation of the plant-specific insert homodimer revealed that increasing the pH of the system to near physiological levels reduced the free energy barrier to dissociation. Furthermore, principal component analysis was used to characterize conformational changes at both acidic and neutral pH. The results indicated that the plant-specific insert may adopt a tertiary structure similar to the characteristic saposin fold and suggest a potential new structural motif among saposin-like proteins. To our knowledge, this acidified PSI structure presents the first example of an alternative saposin-fold motif for any member of the large and diverse SAPLIP family. 相似文献
94.
Summary The xylanolytic and cellulolytic activity fromCellulomanas were reduced by high O2 concentrations in continous culture as well as by an air flow passed trough the samples, suggesting an inhibition or inactivation of enzymes in such conditions. 相似文献
95.
J. De Rudder J. Leclerc M Mercier G. Gosselin J. L. Imbach 《Nucleosides, nucleotides & nucleic acids》2013,32(1-2):221-223
Abstract D-Xylo and Lyxofuranonucleosides have not been extensively studied. Therefore in order to perform a systematic Structure-Antiviral Activity Relationship of the nucleoside analogs we have first synthesized their α and β anomers, some of them being unknown or their structure doubtful in the literature. 相似文献
96.
Abstract. Gas exchange, leaf-nitrogen concentration and water potential were measured in early and late spring in early successional herbaceous plants occurring after cutting and after fire, and in mature woody species from the Mediterranean climax community Quercetum ilicis in central Italy. Net photosynthesis peaked in early spring in all species studied when values for temperature and light were lower but leaf-nitrogen content was higher as compared to late spring, suggesting that nitrogen more than energy input controlled photosynt-hetic rates. Herbaceous pioneer species occurring after cutting showed higher field photo synthetic capacity than evergreen climax trees and shrubs. By contrast, net photosynthesis of herbaceous species occurring in a persistent stage after fire, was in the same range as that of climax trees. This evidence suggests that carbon-gaining appears to be partly related to the dynamic stage of succession and not solely to the growth form. 相似文献
97.
Elisabeth S. Oliveira Paulo E. P. Leite Maria G. Spillantini † Antonio C. M. Camargo Stephen P. Hunt† 《Journal of neurochemistry》1990,55(4):1114-1121
The subcellular and regional distribution of endo-oligopeptidase (EC 3.4.22.19), an enzyme capable of generating enkephalin by single cleavage from enkephalin-containing peptides, was determined by an enzymatic assay using metorphamide and by immunochemical techniques in the CNS of the rat. The rat CNS contains a membrane-associated form of endo-oligopeptidase, an enzyme predominantly associated with the soluble fraction of brain homogenates. Subcellular fractionation showed that approximately 17% of the total activity of the enzyme is associated with membrane fractions including synaptosomes. Synaptosomal membranes were prepared from neocortex, striatum, hypothalamus, medulla, spinal cord, and cerebellum. The amount of EC 3.4.22.19 activity solubilized by 3-[( 3-cholamidopropyl]dimethylammonio)-1-propanesulfonate from synaptosomal membranes was similar in neocortex, striatum, and hypothalamus, being three- to 10-fold greater than in spinal cord, cerebellum, and medulla. A polyclonal antibody exhibiting high affinity for endo-oligopeptidase was raised in rabbits against the purified rat brain enzyme and used to localize endo-oligopeptidase by Western blotting and by immunoperoxidase techniques. A strong band corresponding to the Mr of EC 3.4.22.19 was found in solubilized proteins obtained from synaptosomal membranes prepared from hypothalamus, neocortex, and striatum when subjected to Western blotting. The immunohistochemical localization of endo-oligopeptidase indicated that the immunoreactivity was confined to gray matter in regions known to be rich in peptide-containing neurons such as the striatum. In the cerebellum, a region poor in peptides, no staining could be detected. The nonuniform distribution of endo-oligopeptidase in rat brain suggests a role in neurotransmitter processing in the CNS. 相似文献
98.
99.
The interaction of jatrophone with sRNA from Escherichia coli has been investigated through UV, CD, and 1H NMR measurements. The results obtained show that the interaction with jatrophone increases the stability of the polynucleotide. It appears that the optical properties of jatrophone depend upon the jatrophone/nucleotide ratio. The observed behaviour can only be explained by the existence of different types of interaction between jatrophone and sRNA. Even for a jatrophone/nucleotide ratio as low as 0.17 the 1H NMR spectra show a multiplicity of resonances that can only be explained by the simultaneous existence of two different binding modes involving the jatrophone molecules. 相似文献
100.
Pollens from Pinus canariensis, P. nigra, P. pinaster, P. pinea, Castanea sativa, Magnolia grandiflora, Olea sativa cv frantoio, cv itrana, cv pisciottana were examined for their free amino acid composition. A large amount of proline was found in all species; pollens of Olea also contain a large amount of serine. 相似文献