全文获取类型
收费全文 | 3138篇 |
免费 | 290篇 |
出版年
2023年 | 12篇 |
2022年 | 22篇 |
2021年 | 53篇 |
2020年 | 34篇 |
2019年 | 41篇 |
2018年 | 38篇 |
2017年 | 64篇 |
2016年 | 100篇 |
2015年 | 182篇 |
2014年 | 196篇 |
2013年 | 219篇 |
2012年 | 272篇 |
2011年 | 276篇 |
2010年 | 186篇 |
2009年 | 127篇 |
2008年 | 199篇 |
2007年 | 212篇 |
2006年 | 190篇 |
2005年 | 196篇 |
2004年 | 128篇 |
2003年 | 130篇 |
2002年 | 104篇 |
2001年 | 43篇 |
2000年 | 37篇 |
1999年 | 37篇 |
1998年 | 22篇 |
1997年 | 15篇 |
1996年 | 16篇 |
1995年 | 19篇 |
1994年 | 10篇 |
1993年 | 6篇 |
1992年 | 14篇 |
1991年 | 16篇 |
1990年 | 13篇 |
1989年 | 18篇 |
1988年 | 19篇 |
1987年 | 21篇 |
1986年 | 10篇 |
1985年 | 14篇 |
1984年 | 9篇 |
1983年 | 5篇 |
1981年 | 8篇 |
1978年 | 6篇 |
1976年 | 5篇 |
1973年 | 11篇 |
1972年 | 6篇 |
1971年 | 9篇 |
1968年 | 5篇 |
1966年 | 5篇 |
1963年 | 4篇 |
排序方式: 共有3428条查询结果,搜索用时 31 毫秒
131.
Identification of a streptococcal octapeptide motif involved in acute rheumatic fever 总被引:1,自引:0,他引:1
Dinkla K Nitsche-Schmitz DP Barroso V Reissmann S Johansson HM Frick IM Rohde M Chhatwal GS 《The Journal of biological chemistry》2007,282(26):18686-18693
Acute rheumatic fever is a serious autoimmune sequela of pharyngitis caused by certain group A streptococci. One mechanism applied by streptococcal strains capable of causing acute rheumatic fever is formation of an autoantigenic complex with human collagen IV. In some geographic regions with a high incidence of acute rheumatic fever pharyngeal carriage of group C and group G streptococci prevails. Examination of such strains revealed the presence of M-like surface proteins that bind human collagen. Using a peptide array and recombinant proteins with targeted amino acid substitutions, we could demonstrate that formation of collagen complexes during streptococcal infections depends on an octapeptide motif, which is present in collagen binding M and M-like proteins of different beta-hemolytic streptococcal species. Mice immunized with streptococcal proteins that contain the collagen binding octapeptide motif developed high serum titers of anti-collagen antibodies. In sera of rheumatic fever patients such a collagen autoimmune response was accompanied by specific reactivity against the collagen-binding proteins, linking the observed effect to clinical cases. Taken together, the data demonstrate that the identified octapeptide motif through its action on collagen plays a crucial role in the pathogenesis of rheumatic fever. Eradication of streptococci that express proteins with the collagen binding motif appears advisable for controlling rheumatic fever. 相似文献
132.
Objective: Recent studies have shown that free fatty acid (FFA) release is pulsatile and that this pattern is controlled by the sympathetic nervous system. It is, then, necessary to understand and characterize adipose tissue lipolysis to elucidate its effect on metabolism. In this study, we introduce deconvolution as a method to detect and quantify pulsatile FFA release. Research Methods and Procedures: Octanoate, a medium‐chain fatty acid, was infused in male mongrel dogs (n = 7) to mimic the pulsatile appearance of plasma FFAs. Deconvolution analysis was used to reconstruct the number and timing of infused octanoate pulses from plasma FFA concentrations. Results: Deconvolution analysis was able to reconstruct the exogenously infused pulses of octanoate used to mimic pulsatile appearance of FFAs (pulse frequency, 8 per hour; interpulse interval, 7 minutes). However, determination of pulse mass was less accurate (1.0 ± 0.0 vs. 0.54 ± 0.1 mM). The addition of varying levels of Gaussian noise to non‐oscillatory FFA time series did not lead to detection of extraneous FFA pulses. However, goodness of fit declined with increasing variability. Discussion: These results support the use of deconvolution as an accurate approach to determine the temporal sequence of endogenous FFA release. 相似文献
133.
134.
Zakhartsev M Lucassen M Kulishova L Deigweiher K Smirnova YA Zinov'eva RD Mugue N Baklushinskaya I Pörtner HO Ozernyuk ND 《The FEBS journal》2007,274(6):1503-1513
Temperature acclimation in poikilotherms entails metabolic rearrangements provided by variations in enzyme properties. However, in most cases the underlying molecular mechanisms that result in structural changes in the enzymes are obscure. This study reports that acclimation to low (5 degrees C) and high (18 degrees C) temperatures leads to differential expression of alternative forms of the LDH-A gene in white skeletal muscle of weatherfish, Misgurnus fossilis. Two isoforms of LDH-A mRNA were isolated and characterized: a short isoform (= 1332 bp) and a long isoform ( = 1550 bp), which both have 5'-UTRs and ORFs of the same length (333 amino acid residues), but differ in the length of the 3'-UTR. In addition, these two mRNAs have 44 nucleotide point mismatches of an irregular pattern along the complete sequence, resulting in three amino acid mismatches (Gly214Val; Val304Ile and Asp312Glu) between protein products from the short and long mRNA forms, correspondingly LDH-A(alpha) and LDH-A(beta) subunits. It is expected that the beta-subunit is more aliphatic due to the properties of the mismatched amino acids and therefore sterically more restricted. According to molecular modelling of M. fossilis LDH-A, the Val304Ile mismatch is located in the subunit contact area of the tetramer, whereas the remaining two mismatches surround the contact area; this is expected to manifest in the kinetic and thermodynamic properties of the assembled tetramer. In warm-acclimated fish the relative expression between alpha and beta isoforms of the LDH-A mRNA is around 5 : 1, whereas in cold-acclimated fish expression of is reduced almost to zero. This indicates that at low temperature the pool of total tetrameric LDH-A is more homogeneous in terms of alpha/beta-subunit composition. The temperature acclimation pattern of proportional pooling of subunits with different kinetic and thermodynamic properties of the tetrameric enzyme may result in fine-tuning of the properties of skeletal LDH-A, which is in line with previously observed kinetic and thermodynamic differences between 'cold' and 'warm' LDH-A purified from weatherfish. Also, an irregular pattern of nucleotide mismatches indicates that these mRNAs are the products of two independently evolving genes, i.e. paralogues. Karyotype analysis has confirmed that the experimental population of M. fossilis is tetraploid (2n = 100), therefore gene duplication, possibly through tetraploidy, may contribute to the adaptability towards temperature variation. 相似文献
135.
The plastid-encoded psaJ gene encodes a hydrophobic low-molecular-mass subunit of photosystem I (PSI) containing one transmembrane helix. Homoplastomic transformants with an inactivated psaJ gene were devoid of PSI-J protein. The mutant plants were slightly smaller and paler than wild-type because of a 13% reduction in chlorophyll content per leaf area caused by an approximately 20% reduction in PSI. The amount of the peripheral antenna proteins, Lhca2 and Lhca3, was decreased to the same level as the core subunits, but Lhca1 and Lhca4 were present in relative excess. The functional size of the PSI antenna was not affected, suggesting that PSI-J is not involved in binding of light-harvesting complex I. The specific PSI activity, measured as NADP(+) photoreduction in vitro, revealed a 55% reduction in electron transport through PSI in the mutant. No significant difference in the second-order rate constant for electron transfer from reduced plastocyanin to oxidized P700 was observed in the absence of PSI-J. Instead, a large fraction of PSI was found to be inactive. Immunoblotting analysis revealed a secondary loss of the luminal PSI-N subunit in PSI particles devoid of PSI-J. Presumably PSI-J affects the conformation of PSI-F, which in turn affects the binding of PSI-N. This together renders a fraction of the PSI particles inactive. Thus, PSI-J is an important subunit that, together with PSI-F and PSI-N, is required for formation of the plastocyanin-binding domain of PSI. PSI-J is furthermore important for stability or assembly of the PSI complex. 相似文献
136.
137.
Many classes of non-coding RNAs (ncRNAs; including Y RNAs, vault RNAs, RNase P RNAs, and MRP RNAs, as well as a novel class recently discovered in Dictyostelium discoideum) can be characterized by a pattern of short but well-conserved sequence elements that are separated by poorly conserved regions of sometimes highly variable lengths. Local alignment algorithms such as BLAST are therefore ill-suited for the discovery of new homologs of such ncRNAs in genomic sequences. The Fragrep tool instead implements an efficient algorithm for detecting the pattern fragments that occur in a given order. For each pattern fragment, the mismatch tolerance and bounds on the length of the intervening sequences can be specified separately. Furthermore, matches can be ranked by a statistically well-motivated scoring scheme. 相似文献
138.
139.
Studies with protein kinase C inhibitors presently available cannot elucidate the role of protein kinase C in the activation of NADPH oxidase 总被引:2,自引:0,他引:2
The effects of various protein kinase C (PKC) inhibitors on NADPH oxidase (NO) activation by the phorbol ester PMA and by the chemotactic peptide FMLP were studied. H-7 reduced the effects of both stimuli in human neutrophils (HN) and HL-60 cells by 13-63%. Polymyxin B did not inhibit NO activation by PMA and FMLP in HN and reduced the effects of both stimuli in HL-60 cells by 27-55%. Retinal and retinoic acid enhanced the effects of PMA and FMLP in HL-60 cells and of FMLP in HN up to 4.5-fold. In contrast, retinoic acid inhibited the effect of PMA in HN. In the presence of cytochalasin B, retinal inhibited the effect of FMLP in HN, whereas retinoic acid inhibited NO activation by FMLP in both cell types. The dual PKC/calmodulin inhibitors trifluoperazine and W-7 abolished NO activation by PMA and FMLP in HN and HL-60 cells. Thus, the effects of PKC inhibitors on NO activation exhibit (1) cell type specificity, (2) stimulus dependency and (3) no correlation with in vitro inhibition of PKC. Our results suggest that studies with PKC inhibitors presently available cannot clarify the role of PKC in NO activation. 相似文献
140.