全文获取类型
收费全文 | 7847篇 |
免费 | 658篇 |
国内免费 | 6篇 |
专业分类
8511篇 |
出版年
2023年 | 28篇 |
2022年 | 81篇 |
2021年 | 122篇 |
2020年 | 63篇 |
2019年 | 109篇 |
2018年 | 153篇 |
2017年 | 113篇 |
2016年 | 237篇 |
2015年 | 363篇 |
2014年 | 424篇 |
2013年 | 436篇 |
2012年 | 551篇 |
2011年 | 559篇 |
2010年 | 348篇 |
2009年 | 328篇 |
2008年 | 450篇 |
2007年 | 433篇 |
2006年 | 393篇 |
2005年 | 396篇 |
2004年 | 399篇 |
2003年 | 349篇 |
2002年 | 313篇 |
2001年 | 303篇 |
2000年 | 242篇 |
1999年 | 214篇 |
1998年 | 76篇 |
1997年 | 79篇 |
1996年 | 58篇 |
1995年 | 57篇 |
1994年 | 37篇 |
1993年 | 27篇 |
1992年 | 77篇 |
1991年 | 83篇 |
1990年 | 50篇 |
1989年 | 54篇 |
1988年 | 46篇 |
1987年 | 44篇 |
1986年 | 32篇 |
1985年 | 35篇 |
1984年 | 33篇 |
1982年 | 20篇 |
1981年 | 17篇 |
1979年 | 19篇 |
1978年 | 22篇 |
1977年 | 23篇 |
1976年 | 24篇 |
1974年 | 24篇 |
1973年 | 19篇 |
1971年 | 20篇 |
1970年 | 17篇 |
排序方式: 共有8511条查询结果,搜索用时 15 毫秒
931.
Mutational study of the bacterial hemoglobin distal heme pocket 总被引:1,自引:0,他引:1
Verma S Patel S Kaur R Chung YT Duk BT Dikshit KL Stark BC Webster DA 《Biochemical and biophysical research communications》2005,326(2):290-297
Ligand binding experiments on three mutants in the distal heme pocket of Vitreoscilla hemoglobin (GlnE7His, ProE8Ala, and GlnE7His,ProE8Ala) were used to probe the role of GlnE7 and ProE8 in the pocket's unusual structure. The oxygen dissociation constants for the wild type, E8Ala mutant, and E7His mutant proteins were 4.5, 4.7, and 1.7microM, respectively; the K(d) for the double mutant was not determinable by our technique. Visible-Soret spectra of the carbonyl and cyanyl forms and FT-IR of the carbonyl form of the E8 mutant were similar to those of the wild type; the opposite was true for the GlnE7His and GlnE7His,ProE8Ala mutants, which also differed from wild type in the visible-Soret spectra of their oxidized forms. Models of the effects of the mutations on distal pocket structure were consistent with the experimental findings, particularly the larger effects of the GlnE7His change. 相似文献
932.
Lee SH Ahn SJ Im YJ Cho K Chung GC Cho BH Han O 《Biochemical and biophysical research communications》2005,330(4):1194-1198
Previous studies show that low temperature strongly induces suberin layers in the roots of chilling-sensitive cucumber plants, while in contrast, low temperature produces a much weaker induction of suberin layers in the roots of the chilling-tolerant figleaf gourd [S.H. Lee, G.C. Chung, S. Steudle, Gating of aquaporins by low temperature in roots of chilling-sensitive cucumber and -tolerant figleaf gourd, J. Exp. Bot. 56 (2005) 985-995; S.H. Lee, G.C. Chung, E. Steudle, Low temperature and mechanical stresses differently gate aquaporins of root cortical cells of chilling-sensitive cucumber and figleaf gourd, Plant Cell Environ. (2005) in press; S.J. Ahn, Y.J. Im, G.C. Chung, B.H. Cho, S.R. Suh, Physiological responses of grafted-cucumber leaves and rootstock roots affected by low root temperature, Scientia Hort. 81 (1999) 397-408]. Here, the effect of low temperature on fatty acid unsaturation and lipoxygenase activity was examined in cucumber and figleaf gourd. The double bond index demonstrated that membrane lipid unsaturation shows hyperbolic saturation curve in figleaf gourd roots while a biphasic response in cucumber roots to low temperature. In figleaf gourd, the hyperbolic response in the double bond index was primarily due to accumulation of linolenic acid. Chilling stress also significantly induced lipoxygenase activity in figleaf gourd roots. These results suggest that the degree of unsaturation of root plasma membrane lipids correlates positively with chilling-tolerance. Therefore, studies that compare the effects of chilling on cucumber and figleaf gourd may provide broad insight into stress response mechanisms in chilling-sensitive and chilling-tolerant plants. Furthermore, these studies may provide important information regarding the relationship between lipid unsaturation and lipoxygenase function/activity, and between lipoxygenase activity and water channeling during the response to chilling stress. The possible roles of these processes in chilling tolerance are discussed. 相似文献
933.
The present study examined the hypothesis that inhibition of myometrial gap junctions through MAPK1-induced phosphorylation of GJA1 (connexin43) leads to inhibition of spontaneous phasic uterine contractions by 2,2'-dichlorobiphenyl (2,2'-DCB). Uterine strips from Gestation Day 10-pregnant rats exposed in muscle baths to 2,2'-DCB exhibited increased oscillatory frequency and decreased amplitude and synchronization of contractions. To assess effects on gap junctions, Lucifer yellow was injected into myometrial cells and transfer to adjacent cells was scored. After a 1-h treatment, 100 microM 2,2'-DCB decreased Lucifer yellow intercellular transfer in a concentration-dependent manner. The MAP2K1 inhibitor PD98059 increased percentage of dye transfer to adjacent myometrial cells from 18% in cultures exposed for 1 h to 100 microM 2,2'-DCB alone to 48% in cultures cotreated with 50 microM PD98059 and 100 microM 2,2'-DCB. In contrast, the conventional PRKC inhibitor G?6976 (10 microM) had no significant effect on 2,2'-DCB-induced inhibition of dye transfer. Western blotting showed about a 4.5-fold increase in phosphorylation of GJA1 at S255, a MAPK1 site, after exposure to 100 microM 2,2'-DCB compared to untreated and solvent controls. However, there was no difference in phosphorylation of GJA1 at S368, a PRKC site. Cells treated with 2,2'-DCB increased phosphorylated MAPK1, implicating the increase of activation of MAPK1. Cotreatment with 100 microM 2,2'-DCB and 5 microM PD98059 reversed 2,2'-DCB-induced modification of uterine contractions and increase of pGJA1(S255) in uterine strips. Therefore, this study suggests that 2,2'-DCB decreases amplitude and synchronization of uterine contractions mediated through MAPK1-mediated phosphorylation of GJA1 and subsequent inhibition of myometrial gap junctions. 相似文献
934.
Bcl-2 expression suppresses mismatch repair activity through inhibition of E2F transcriptional activity 总被引:7,自引:0,他引:7
Youn CK Cho HJ Kim SH Kim HB Kim MH Chang IY Lee JS Chung MH Hahm KS You HJ 《Nature cell biology》2005,7(2):137-147
Bcl-2 stimulates mutagenesis after the exposure of cells to DNA-damaging agents. However, the biological mechanisms of Bcl-2-mediated mutagenesis have remained largely obscure. Here we demonstrate that the Bcl-2-mediated suppression of hMSH2 expression results in a reduced cellular capacity to repair mismatches. The pathway linking Bcl-2 expression to the suppression of mismatch repair (MMR) activity involves the hypophosphorylation of pRb, and then the enhancement of the E2F-pRb complex. This is followed by a decrease in hMSH2 expression. MMR has a key role in protection against deleterious mutation accumulation and in maintaining genomic stability. Therefore, the decreased MMR activity by Bcl-2 may be an underlying mechanism for Bcl-2-promoted oncogenesis. 相似文献
935.
Shi J Du J Ma T Pankiewicz KW Patterson SE Hassan AE Tharnish PM McBrayer TR Lostia S Stuyver LJ Watanabe KA Chu CK Schinazi RF Otto MJ 《Nucleosides, nucleotides & nucleic acids》2005,24(5-7):875-879
Based on the discovery of beta-D-2'-deoxy-2'-fluorocytidine as a potent anti-hepatitis C virus (HCV) agent, a series of beta-D- and L-2'-deoxy-2'-fluoroibonucleosides with modifications at 5 and/or 4 positions were synthesized and evaluated for their in vitro activity against HCV and bovine viral diarrhea virus (BVDV). The introduction of the 2'-fluoro group was achieved by either fluorination of 2,2'-anhydronucleosides with hydrogen fluoride-pyridine or potassium fluoride, or a fluorination of arabinonucleosides with DAST. Among the 27 analogues synthesized, only the 5-fluoro compounds, namely beta-D-2'-deoxy-2',5-difluorocytidine (5), had anti-HCV activity in the subgenomic HCV replicon cell line, and inhibitory activity against ribosomal RNA. As beta-D-N4-hydroxycytidine (NHC) had previously shown potent anti-HCV activity, the two functionalities of the N4-hydroxyl and the 2'-fluoro were combined into one molecule, yielding beta-D-2'-deoxy-2'-fluoro-N4-hydroxycytidine (12). However, this nucleoside showed neither anti-HCV activity nor toxicity. All the L-forms of the analogues were devoid of anti-HCV activity. None of the compounds showed anti-BVDV activity, suggesting that the BVDV system cannot reliably predict anti-HCV activity in vitro. 相似文献
936.
Since the discovery of 3'-azido-3'-deoxythymidine (AZT) and 2',3'-didehydro-2',3'-dideoxythymidine (d4T) as potent and selective inhibitors of the replication of human immunodeficiency virus (HIV), there has been a growing interest for the synthesis of 2',3'-didehydro-2',3'dideoxynucleosides with electron withdrawing groups on the sugar moiety. Here we described an efficient method for the synthesis of such nucleoside analogs bearing structural features of both AZT and d4T The key intermediate, 3-azido-1,2-bis-O-acetyl-5-O-benzoyl-3-deoxy-D-ribofuranose, 5 was synthesized from commercially available D-xylose in five steps, from which a series of pyrimidine and purine nucleosides were synthesized in high yields. The resultant protected nucleosides were converted to target nucleosides using appropriate chemical modifications. The final nucleosides were evaluated as potential anti-HIV agents. 相似文献
937.
938.
Lee HW Won KJ Cho SH Ha YH Park WS Yim HT Baek M Rew JH Yoon SH Yim SV Chung JH Lee KT 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2005,821(2):215-220
A rapid and simple HPLC method with UV detection (288 nm) was developed and validated for quantitation of niflumic acid in human plasma, the active metabolite of talniflumate. After precipitation with 100% methanol containing the internal standard, indomethacin, the analysis of the niflumic acid level in the plasma samples was carried out using a reverse phase C18 CAPCELL PAK (5 microm, 4.6 mm x 250 mm) column. The chromatographic separation was accomplished with an isocratic mobile phase consisting of a mixture of 0.1M sodium acetate in water and acetonitrile (37:63, v/v), adjusted to pH 6.4. This HPLC method was validated by examining its precision and accuracy for inter- and intra-day runs in a linear concentration range of 0.02-5.00 microg/mL. Stability of niflumic acid in plasma was excellent, with no evidence of degradation during sample processing (autosampler) and 30 days storage in a freezer. This validated method was successfully applied to the bioequivalence study of talniflunate in healthy volunteers. 相似文献
939.
Sung H Chul Han K Chul Kim J Wan Oh K Su Yoo H Tae Hong J Bok Chung Y Lee CK Lee KS Song S 《FEMS yeast research》2005,5(10):943-950
Functional analysis of genes from Saccharomyces cerevisiae has been the major goal after determination of genome sequences. Even though several tools for molecular-genetic analyses have been developed, only a limited number of reliable genetic tools are available to support functional assay at protein level. Epitope tagging is a powerful tool for detecting, purifying, and functional studying of proteins. But systematic tagging systems developed with integration vectors are not available. Here, we have constructed a set of integration vectors allowing a translational fusion of interested proteins to the four different epitope tags (HA, Myc, Flag, and GFP). To confirm function and expression of C-terminal-tagged proteins, we used Cdc11, a component of the septin filament that encircles the mother bud neck and consists of five major proteins: Cdc3, Cdc10, Cdc11, Cdc12, and Sep7. The tagged version of Cdc11 expressed under its endogenous promoter was found to be physiologically functional, as evidenced by localization at the neck and suppression of the growth defect associated with the temperature-sensitive mutation of cdc11-6. The expressed proteins were efficiently detected with antibodies against Cdc11 or the epitopes. When immunoprecipitated with anti-Myc antibody, each septin protein tagged with Myc was effectively copurified with other septin components, indicating formation of a stable septin complex. Because the modules of the tags were located under the same array of eighteen restriction sites on integration vectors containing four different markers (HIS3, TRP1, LEU2, or URA3), this tagging system provides efficient multiple tagging and stable expression of a gene of interest. 相似文献
940.
Cheng CH Chung MC Liu SM Chen SK Kao FY Lin SJ Hsiao SH Tseng IC Hsing YI Wu HP Chen CS Shaw JF Wu J Matsumoto T Sasaki T Chen HH Chow TY 《Molecular genetics and genomics : MGG》2005,274(4):337-345
A fine physical map of the rice (Oryza sativa spp. Japonica var. Nipponbare) chromosome 5 with bacterial artificial chromosome (BAC) and PI-derived artificial chromosome (PAC) clones
was constructed through integration of 280 sequenced BAC/PAC clones and 232 sequence tagged site/expressed sequence tag markers
with the use of fingerprinted contig data of the Nipponbare genome. This map consists of five contigs covering 99% of the
estimated chromosome size (30.08 Mb). The four physical gaps were estimated at 30 and 20 kb for gaps 1–3 and gap 4, respectively.
We have submitted 42.2-Mb sequences with 29.8 Mb of nonoverlapping sequences to public databases. BAC clones corresponding
to telomere and centromere regions were confirmed by BAC-fluorescence in situ hybridization (FISH) on a pachytene chromosome.
The genetically centromeric region at 54.6 cM was covered by a minimum tiling path spanning 2.1 Mb with no physical gaps.
The precise position of the centromere was revealed by using three overlapping BAC/PACs for ~150 kb. In addition, FISH results
revealed uneven chromatin condensation around the centromeric region at the pachytene stage. This map is of use for positional
cloning and further characterization of the rice functional genomics.
Electronic supplementary material Supplementary material is available in the online version of this article at
and is accessible for authorized users.
Chia-Hsiung Cheng and Mei-Chu Chung have equal contributions. 相似文献