全文获取类型
收费全文 | 6940篇 |
免费 | 257篇 |
国内免费 | 377篇 |
出版年
2023年 | 57篇 |
2022年 | 95篇 |
2021年 | 115篇 |
2020年 | 150篇 |
2019年 | 215篇 |
2018年 | 181篇 |
2017年 | 134篇 |
2016年 | 186篇 |
2015年 | 191篇 |
2014年 | 389篇 |
2013年 | 564篇 |
2012年 | 208篇 |
2011年 | 380篇 |
2010年 | 295篇 |
2009年 | 385篇 |
2008年 | 423篇 |
2007年 | 400篇 |
2006年 | 361篇 |
2005年 | 331篇 |
2004年 | 248篇 |
2003年 | 254篇 |
2002年 | 260篇 |
2001年 | 132篇 |
2000年 | 116篇 |
1999年 | 122篇 |
1998年 | 105篇 |
1997年 | 97篇 |
1996年 | 76篇 |
1995年 | 93篇 |
1994年 | 101篇 |
1993年 | 93篇 |
1992年 | 82篇 |
1991年 | 60篇 |
1990年 | 51篇 |
1989年 | 61篇 |
1988年 | 43篇 |
1987年 | 46篇 |
1986年 | 34篇 |
1985年 | 69篇 |
1984年 | 112篇 |
1983年 | 78篇 |
1982年 | 42篇 |
1981年 | 46篇 |
1980年 | 30篇 |
1979年 | 12篇 |
1978年 | 15篇 |
1977年 | 8篇 |
1976年 | 12篇 |
1975年 | 6篇 |
1973年 | 4篇 |
排序方式: 共有7574条查询结果,搜索用时 15 毫秒
911.
《Bioorganic & medicinal chemistry letters》2014,24(21):5127-5133
The correct positioning and orientation of an hydrogen bond acceptor (HBA) in the tail portion of the biaryl series of CRTh2 antagonists is a requirement for long receptor residence time. The HBA in combination with a small steric substituent in the core section (Rcore ≠ H) gives access to compounds with dissociation half-lives of ⩾24 h. 相似文献
912.
In the non-heterocyst, marine cyanobacterium Trichodesmium nitrogen fixation is confined to the photoperiod and occurs coevally with oxygenic photosynthesis although nitrogenase is irreversibly inactivated by oxygen. In previous studies it was found that regulation of photosynthesis for nitrogen fixation involves Mehler reaction and various activity states with reversible coupling of photosynthetic components. We now investigated these activity states in more detail. Spectrally resolved fluorescence kinetic measurements of single cells revealed that they were related to alternate uncoupling and coupling of phycobilisomes from and to the photosystems, changing the effective cross-section of PSII. Therefore, we isolated and purified the phycobiliproteins of Trichodesmium via ion exchange chromatography and recorded their UV/VIS absorption, fluorescence excitation and fluorescence emission spectra. After describing these spectra by mathematical equations via the Gauss-Peak-Spectra method, we used them to deconvolute the in vivo fluorescence spectra of Trichodesmium cells. This revealed that the contribution of different parts of the phycobilisome antenna to fluorescence quenching changed during the daily activity cycle, and that individual phycobiliproteins can be reversibly coupled to the photosystems, while the expression levels of these proteins did not change much during the daily activity cycle. Thus we propose that variable phycobilisome coupling plays a key role in the regulation of photosynthesis for nitrogen fixation in Trichodesmium. 相似文献
913.
F.A. Baglia S.-W. Kwan G.M. Fuller 《Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression》1982,696(1):107-113
A quantitative enzyme-linked immunosorbent assay was developed and utilized to study the stimulation of haptoglobin biosynthesis during an acute inflammatory challenge. A 10-fold increase in intracellular haptoglobin was measured at the peak of the inflammatory response. The increase in serum haptoglobin levels was concomitant with the intracellular levels, demonstrating the secretory output is also elevated during the inflammatory period. A monospecific antihaptoglobin was produced and used to detect the specific polysomes involved in haptoglobin synthesis. The amount of radioactively labeled antibody bound to the nascent haptoglobin chain was increased approx. 3-fold during the inflammatory response, indicating that new haptoglobin was being synthesized and suggesting an increase in functional haptoglobin mRNA resulting from the inflammatory signal. 相似文献
914.
Four series of para or meta - substituted thiazolylbenzenesulfonamides bearing Cl substituents were designed, synthesized, and evaluated as inhibitors of all 12 catalytically active recombinant human carbonic anhydrase (CA) isoforms. Observed affinities were determined by the fluorescent thermal shift assay and the intrinsic affinities were calculated based on the fractions of binding-ready deprotonated sulfonamide and CA bearing protonated hydroxide bound to the catalytic Zn(II) in the active site. Several compounds exhibited selectivity towards CA IX, an anticancer target. Intrinsic affinities reached 30 pM, while the observed affinities - 70 nM. The structure-intrinsic affinity relationship map of the compounds showed the energetic contributions of the thiazole ring and its substituents. 相似文献
915.
Hyun-Jin Kang Tuong Vy Thi Le Kyungmin Kim Jeonghwan Hur Kyeong Kyu Kim Hyun-Ju Park 《Journal of molecular biology》2014
Both G-quadruplex and Z-DNA can be formed in G-rich and repetitive sequences on genome, and their formation and biological functions are controlled by specific proteins. Z-DNA binding proteins, such as human ADAR1, have a highly conserved Z-DNA binding domain having selective affinity to Z-DNA. Here, our study identifies the Z-DNA binding domain of human ADAR1 (hZαADAR1) as a novel G-quadruplex binding protein that recognizes c-myc promoter G-quadruplex formed in NHEIII1 region and represses the gene expression. An electrophoretic migration shift assay shows the binding of hZαADAR1 to the intramolecular c-myc promoter G-quadruplex-forming DNA oligomer. To corroborate the binding of hZαADAR1 to the G-quadruplex, we conducted CD and NMR chemical shift perturbation analyses. CD results indicate that hZαADAR1 stabilizes the parallel-stranded conformation of the c-myc G-quadruplex. The NMR chemical shift perturbation data reveal that the G-quadruplex binding region in hZαADAR1 was almost identical with the Z-DNA binding region. Finally, promoter assay and Western blot analysis show that hZαADAR1 suppresses the c-myc expression promoted by NHEIII1 region containing the G-quadruplex-forming sequence. This finding suggests a novel function of Z-DNA binding protein as a regulator of G-quadruplex-mediated gene expression. 相似文献
916.
Multitargeting involves the application of molecules that are deliberately intended to bind to two or more unrelated cellular targets with high affinity. In epigenetic chemical biology and drug discovery, the rational design of multitargeting agents has evolved to a sophisticated level, and there are now five examples that have reached clinical trials. This review covers recent developments in the field and future prospects. 相似文献
917.
Unconsidered factors affecting hydrogenase activity measurement 总被引:1,自引:0,他引:1
The effects of sample geometry and enzyme concentration on the H2-evolving activity of hydrogenase from Thiocapsa roseopersicina was measured. The specific activity increased linearly with increasing interface area between the liquid and the gas phase. Enzyme concentration was varied over four orders of magnitude and within this range the apparent specific activity depended on hydrogenase concentration. The experimental findings have been interpreted by a mathematical model involving competing H2 consumption reactions. The observed phenomena interfere with the widely used hydrogenase assay so that most of the previously published specific activity values are underestimated and should be corrected. The systematic error due to these hitherto unspecified parameters can easily exceed 10 000%; therefore, a thorough standardization of the assay procedure is necessary in order to make the data from various laboratories comparable. 相似文献
918.
Nolan W. Kennedy Svetlana P. Ikonomova Marilyn Slininger Lee Henry W. Raeder Danielle Tullman-Ercek 《Journal of molecular biology》2021,433(2):166721
Protein self-assembly is a common and essential biological phenomenon, and bacterial microcompartments present a promising model system to study this process. Bacterial microcompartments are large, protein-based organelles which natively carry out processes important for carbon fixation in cyanobacteria and the survival of enteric bacteria. These structures are increasingly popular with biological engineers due to their potential utility as nanobioreactors or drug delivery vehicles. However, the limited understanding of the assembly mechanism of these bacterial microcompartments hinders efforts to repurpose them for non-native functions. Here, we comprehensively investigate proteins involved in the assembly of the 1,2-propanediol utilization bacterial microcompartment from Salmonella enterica serovar Typhimurium LT2, one of the most widely studied microcompartment systems. We first demonstrate that two shell proteins, PduA and PduJ, have a high propensity for self-assembly upon overexpression, and we provide a novel method for self-assembly quantification. Using genomic knock-outs and knock-ins, we systematically show that these two proteins play an essential and redundant role in bacterial microcompartment assembly that cannot be compensated by other shell proteins. At least one of the two proteins PduA and PduJ must be present for the bacterial microcompartment shell to assemble. We also demonstrate that assembly-deficient variants of these proteins are unable to rescue microcompartment formation, highlighting the importance of this assembly property. Our work provides insight into the assembly mechanism of these bacterial organelles and will aid downstream engineering efforts. 相似文献
919.
920.
Maurizio Sajeva Francesca Grisafi Anna Maria Ferrarella Paolo D'italia 《Plant biosystems》2013,147(5):911-917
Abstract Starch was enzymatically assayed in the hypocotyls of radish (Raphanus sativus L.) seedlings grown in water or chloramphenicol (CAP) 1 × 104. CAP inhibits starch formation and its effect is related to the concentration. Both CAP- and water-grown hypocotyls are able to accumulate starch when sucrose is supplied in the medium, thus suggesting that the damage caused by CAP to the amyloplast is not irreversible. Apical segments of both water- and CAP- grown hypocotyls accumulate starch upon incubation in sucrose solutions while basal segments are unable to accumulate starch even in the presence of sucrose. The authors suggest that the basal segments are unable to perform sucrose uptake or that the amyloplast is incapable to starch synthesis. In any case the inability of the basal segment to perform sucrose uptake is independent of CAP. These findings confirm that the radish hypocotyls is not homogeneous along its axes. 相似文献