全文获取类型
收费全文 | 61475篇 |
免费 | 4629篇 |
国内免费 | 3701篇 |
出版年
2024年 | 34篇 |
2023年 | 676篇 |
2022年 | 848篇 |
2021年 | 1345篇 |
2020年 | 1348篇 |
2019年 | 1741篇 |
2018年 | 1753篇 |
2017年 | 1283篇 |
2016年 | 1467篇 |
2015年 | 2029篇 |
2014年 | 2987篇 |
2013年 | 4003篇 |
2012年 | 2199篇 |
2011年 | 3038篇 |
2010年 | 2404篇 |
2009年 | 3081篇 |
2008年 | 3315篇 |
2007年 | 3380篇 |
2006年 | 3097篇 |
2005年 | 3195篇 |
2004年 | 2999篇 |
2003年 | 2636篇 |
2002年 | 2382篇 |
2001年 | 1692篇 |
2000年 | 1389篇 |
1999年 | 1519篇 |
1998年 | 1345篇 |
1997年 | 1094篇 |
1996年 | 989篇 |
1995年 | 1257篇 |
1994年 | 1171篇 |
1993年 | 1043篇 |
1992年 | 936篇 |
1991年 | 697篇 |
1990年 | 585篇 |
1989年 | 532篇 |
1988年 | 558篇 |
1987年 | 467篇 |
1986年 | 425篇 |
1985年 | 444篇 |
1984年 | 550篇 |
1983年 | 328篇 |
1982年 | 389篇 |
1981年 | 256篇 |
1980年 | 251篇 |
1979年 | 203篇 |
1978年 | 133篇 |
1977年 | 94篇 |
1976年 | 85篇 |
1975年 | 35篇 |
排序方式: 共有10000条查询结果,搜索用时 81 毫秒
71.
Aurélien Sokal Pascal Chappert Giovanna Barba-Spaeth Anais Roeser Slim Fourati Imane Azzaoui Alexis Vandenberghe Ignacio Fernandez Annalisa Meola Magali Bouvier-Alias Etienne Crickx Asma Beldi-Ferchiou Sophie Hue Laetitia Languille Marc Michel Samia Baloul France Noizat-Pirenne Marine Luka Matthieu Mahévas 《Cell》2021,184(5):1201-1213.e14
72.
《Cell》2021,184(17):4531-4546.e26
73.
《Cell》2021,184(20):5215-5229.e17
74.
《Journal of molecular biology》2021,433(9):166889
Septins are an example of subtle molecular recognition whereby different paralogues must correctly assemble into functional filaments important for essential cellular events such as cytokinesis. Most possess C-terminal domains capable of forming coiled coils which are believed to be involved in filament formation and bundling. Here, we report an integrated structural approach which aims to unravel their architectural diversity and in so doing provide direct structural information for the coiled-coil regions of five human septins. Unexpectedly, we encounter dimeric structures presenting both parallel and antiparallel arrangements which are in consonance with molecular modelling suggesting that both are energetically accessible. These sequences therefore code for two metastable states of different orientations which employ different but overlapping interfaces. The antiparallel structures present a mixed coiled-coil interface, one side of which is dominated by a continuous chain of core hydrophilic residues. This unusual type of coiled coil could be used to expand the toolkit currently available to the protein engineer for the design of previously unforeseen coiled-coil based assemblies. Within a physiological context, our data provide the first atomic details related to the assumption that the parallel orientation is likely formed between septin monomers from the same filament whilst antiparallelism may participate in the widely described interfilament cross bridges necessary for higher order structures and thereby septin function. 相似文献
75.
76.
《Journal of molecular biology》2021,433(21):167223
Most eukaryotic transmembrane and secreted proteins contain N-terminal signal peptides that mediate insertion of the nascent translation products into the membrane of the endoplasmic reticulum. After membrane insertion, signal peptides typically are cleaved from the mature protein and degraded. Here, we tested whether a small hydrophobic protein selected for growth promoting activity in mammalian cells retained transforming activity while also acting as a signal peptide. We replaced the signal peptide of the PDGF β receptor (PDGFβR) with a previously described 29-residue artificial transmembrane protein named 9C3 that can activate the PDGFβR in trans. We showed that a modified version of 9C3 at the N-terminus of the PDGFβR can function as a signal peptide, as assessed by its ability to support high level expression, glycosylation, and cell surface localization of the PDGFβR. The 9C3 signal peptide retains its ability to interact with the transmembrane domain of the PDGFβR and cause receptor activation and cell proliferation. Cleavage of the 9C3 signal peptide from the mature receptor is not required for these activities. However, signal peptide cleavage does occur in some molecules, and the cleaved signal peptide can persist in cells and activate a co-expressed PDGFβR in trans. Our finding that a hydrophobic sequence can display signal peptide and transforming activity suggest that some naturally occurring signal peptides may also display additional biological activities by interacting with the transmembrane domains of target proteins. 相似文献
77.
《Journal of molecular biology》2021,433(21):167224
Retinoblastoma-binding protein 1 (RBBP1) is involved in gene regulation, epigenetic regulation, and disease processes. RBBP1 contains five domains with DNA-binding or histone-binding activities, but how RBBP1 specifically recognizes chromatin is still unknown. An AT-rich interaction domain (ARID) in RBBP1 was proposed to be the key region for DNA-binding and gene suppression. Here, we first determined the solution structure of a tandem PWWP-ARID domain mutant of RBBP1 after deletion of a long flexible acidic loop L12 in the ARID domain. NMR titration results indicated that the ARID domain interacts with DNA with no GC- or AT-rich preference. Surprisingly, we found that the loop L12 binds to the DNA-binding region of the ARID domain as a DNA mimic and inhibits DNA binding. The loop L12 can also bind weakly to the Tudor and chromobarrel domains of RBBP1, but binds more strongly to the DNA-binding region of the histone H2A-H2B heterodimer. Furthermore, both the loop L12 and DNA can enhance the binding of the chromobarrel domain to H3K4me3 and H4K20me3. Based on these results, we propose a model of chromatin recognition by RBBP1, which highlights the unexpected multiple key roles of the disordered acidic loop L12 in the specific binding of RBBP1 to chromatin. 相似文献
78.
AYAKO TANAKA YOSHIYUKI KUGA YOSHIAKI TANAKA SHIN G. GOTO HIDEHARU NUMATA SAKIKO SHIGA 《Physiological Entomology》2013,38(3):192-201
Quantities of ecdysteroid are compared in the haemolymph and ovaries of the blowfly Protophormia terraenovae Robineau‐Desvoidy (Diptera: Calliphoridae) under reproductive (LD 18 : 6 h at 25 °C) and diapause (LD 12 : 12 h at 20 °C) conditions. The effects of ablation of the pars intercerebralis or ovaries on ecdysteroid quantities and of ablation of the pars intercerebralis on yolk protein expression are examined. Under reproductive conditions, the levels of ecdysteroid in vitellogenic females are high, although the levels in previtellogenic females and females with mature ovaries are low. Under diapause conditions, there are low quantities of ecdysteroid in both the haemolymph and ovaries. Ecdysteroid titres in the haemolymph are not significantly affected by the removal of the ovaries, suggesting that tissues other than the ovaries are also involved in the production of ecdysteroids. Reproductive females in which the pars intercerebralis of the brain is experimentally ablated have ecdysteroid levels that are not significantly different from sham‐operated or intact females. However, yolk protein expression in the fat body is suppressed after removal of the pars intercerebralis. These results suggest that the suppression of ecdysteroid levels in the haemolymph and ovaries is associated with reproductive diapause, and that the pars intercerebralis could play a role in yolk protein synthesis without mediating ecdysteroid production. 相似文献
79.
《Bioscience, biotechnology, and biochemistry》2013,77(10):1571-1574
Staphylococcus aureus is a pathogen important in causing human infections and intoxication. A sensitive fiber-optic that produces evanescent waves was developed for the detection of protein A, a product secreted only by S. aureus. In the immunosensor, a 40-mV argon-ion laser that generated laser light at 488 nm was used together with plastic optical fiber and antibodies to protein A were physically adsorbed onto the fiber. The principle of the detection involved a sandwich immunoassay with fluorescein isothiocyanate conjugated with anti-(protein A) immunoglobulin G to produce signals of the antigen-antibody reaction. The detection limit was 1 ng of protein A per milliliter. The fiber-optic immunosensor could be used for rapid and specific detection of S. aureus in clinical specimens and foods. 相似文献
80.
《Bioscience, biotechnology, and biochemistry》2013,77(10):1978-1987
ipa-43d is a hypothetical gene identified by the Bacillus subtilis genome project (Mol. Microbiol. 10, 371-384 1993; Nature 390, 249-256 1997). The ipa-43d protein overexpressed in E. coli was purified to homogeneity and its properties were analyzed biochemically. The ipa-43d protein was found to be tightly associated with FMN and to be capable of reducing both nitrofurazone and FMN effectively. Although the ipa-43d protein catalysis obeys the ping-pong Bi-Bi mechanism, catalysis mode was changed to the sequential mechanism upon coupling with the bioluminescent reaction. Database search showed that B. subtilis possessed four genes (ipa-44d, ytmO, yddN, and yvbT), encoding proteins similar in amino acid sequence to LuxA and LuxB of Photobacterium fischeri, and, in particular, ipa-44d is immediately adjacent to the ipa-43d gene on the chromosome. 相似文献