全文获取类型
收费全文 | 4609篇 |
免费 | 396篇 |
国内免费 | 2篇 |
专业分类
5007篇 |
出版年
2022年 | 43篇 |
2021年 | 81篇 |
2020年 | 54篇 |
2019年 | 57篇 |
2018年 | 70篇 |
2017年 | 75篇 |
2016年 | 114篇 |
2015年 | 157篇 |
2014年 | 182篇 |
2013年 | 224篇 |
2012年 | 308篇 |
2011年 | 303篇 |
2010年 | 214篇 |
2009年 | 150篇 |
2008年 | 215篇 |
2007年 | 232篇 |
2006年 | 217篇 |
2005年 | 204篇 |
2004年 | 173篇 |
2003年 | 166篇 |
2002年 | 156篇 |
2001年 | 115篇 |
2000年 | 109篇 |
1999年 | 97篇 |
1998年 | 68篇 |
1997年 | 43篇 |
1996年 | 37篇 |
1995年 | 33篇 |
1994年 | 36篇 |
1993年 | 29篇 |
1992年 | 65篇 |
1991年 | 57篇 |
1990年 | 63篇 |
1989年 | 60篇 |
1988年 | 44篇 |
1987年 | 34篇 |
1986年 | 41篇 |
1985年 | 44篇 |
1984年 | 36篇 |
1983年 | 35篇 |
1982年 | 30篇 |
1981年 | 24篇 |
1980年 | 23篇 |
1979年 | 31篇 |
1978年 | 30篇 |
1977年 | 21篇 |
1976年 | 24篇 |
1975年 | 26篇 |
1974年 | 26篇 |
1973年 | 26篇 |
排序方式: 共有5007条查询结果,搜索用时 0 毫秒
11.
12.
13.
Summary To study the influence of phosphorylation and oxidation on the repeat domains of human Tau protein, we faced the challenge to selectively dimerize two cysteine-containing peptides in the presence of a nearby phosphate group. To this end, we were able to demonstrate the utility of a selective dimerization approach by forming disulfide bonds in unprotected phosphopeptides and extended the methodology to unprotected glycopeptides. Activation of one cysteine of a peptide chain with 2,2-dithiodipyridine and coupling this thiopyridyl-peptide to another peptide chain, containing an unprotected cysteine residue, yielded the mixed dimers in high purities and reasonable yields. Phosphate or sugar side chains on either peptide component remained unaffected during the activation and dimerization processes. While for mixed dimers the activated peptides were isolated by chromatography, homodimers were obtained by a simple one-pot reaction after 1 h. We demonstrate that cysteines can be dimerized in unprotected phosphopeptides and glycopeptides, without any side reactions affecting these posttranslational modifications.Abbreviations DCM
dichloromethane
- DMF
N,N-dimethylformamide
- DTP
2,2-dithiodipyridine
- Fmoc
9-fluorenylmethyloxycarbonyl
- HPLC
high-performance liquid chromatography
- MALDI
matrix-assisted laser desorption/ionization
- MS
mass spectrometry
- NFT
neurofibrillary tangles
- PHF
paired helical filaments
- PKC
protein kinase C
- RP
reversed phase
-
human Tau protein
- TFA
trifluoroacetic acid
Parts of this paper were presented at the 24th European Peptide Symposium in Edinburgh, Scotland, U.K., September 8–13, 1996. 相似文献
14.
M K Hoffmann S Koenig R S Mittler H F Oettgen P Ralph C Galanos U Hammerling 《Journal of immunology (Baltimore, Md. : 1950)》1979,122(2):497-502
Peritoneal macrophages of the mouse produce, in response to cell wall components of Gram-negative bacteria (lipopolysaccharide and lipoproteins), a factor that causes antigen-stimulated B cells of differentiate into antibody-producing cells. Unlike lipopolysaccharide, this factor is not mitogenic for B cells. Production of the macrophage factor does not depend on participation of T cells or other accessory cells since it is readily produced by several cloned macrophage cell lines as well as by peritoneal macrophages of athymic nude mice. The factor is active only in conjunction with antigen. T cells, although apparently not necessary, amplify its effect. The factor induces phenotypic differentiation of B cell precursors as selectively as thymopoietin induces differentiation of prothymocytes. 相似文献
15.
A method was elaborated by which the pH in leaf apoplast can be measured. The technique is based on the pH dependent fluorescence of 5-carboxyfluorescein (5-CF) or fluorescein isothiocyanate (FITC). The fluorescein isothiocyanate is coupled with a macromolecular dextran molecule (FITC-dextran). For eliminating the effect of the absolute dye concentration the dual excitation technique was applied. It was shown that the ratio of fluorescence excited by light of 491 nm and 463 nm was virtually independent of the concentration of 5-CF and that this fluorescence ratio was related to the pH. The plasmalemma is practically impermeable to FITC-dextran and in the test we carried out over a period of 6 h not the slightest indication was found that it may penetrate the plasma membrane. For 5-CF this cannot be ruled out completely. It is possible that at pH values below 4.5 it may penetrate biological membranes at low rates.
Experiments with leaves of sunflower ( Helianthus animus cv. Erika) perfused with 5-carboxyfluorescein and supplied with different nitrogen forms showed that NH+ 4 application resulted in a decrease and NO+ 3 application in an increase of the leaf apoplast pH. Leaf spraying with fasicoccin was followed by a pH decrease, while leaf spraying with the protonophores p -trifluoromethoxy carbonytcyanide phenylhydra-zon (FCCP) or nigericin resulted in neutral apoplastic pH. These results provide evidence that the method is well suited for measuring the response of the leaf apoplast pH to changing physiological conditions. 相似文献
Experiments with leaves of sunflower ( Helianthus animus cv. Erika) perfused with 5-carboxyfluorescein and supplied with different nitrogen forms showed that NH
16.
K. H. Hoffmann K. Weidner M. Seidel 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1992,162(8):731-739
Summary Ovaries from 4-day-old female adults of Gryllus bimaculatus produce about 5 ng of free and conjugated ecdysteroids per hour during a 16-h incubation in Grace's medium. During incubation of pieces of the abdominal integument together with the adjacent segmental fat body, a net synthesis of moulting hormones is observed (2.3 ng per hour per animal), similar to that in the ovary. Separate incubations of disunited abdominal epidermis and segmental fat body tissue result in much lower rates of ecdysteroid synthesis. Ecdysteroid synthesis in ovarian homogenates is about one-third of that in intact organs. This reduction is due to a lack of conjugate formation in homogenates. Homogenates of the abdominal integument complex are no longer capable of synthesizing ecdysteroids. For both tissues, a de novo synthesis of ecdysteroids is corroborated by following the in vitro incorporation of [14C]-label from cholesterol and [3H]-label from 2,22,25-trideoxyecdysone (5-ketodiol), respectively, into free ecdysone. The rate of incorporation into ecdysone is only 0.0014% for cholesterol but 0.48% for 5-ketodiol. Both tissues represent primary sources of ecdysteroids in female adult crickets.Abbreviations HPLC
high performance liquid chromatography
- IU
international units
- NP
normal phase
- RIA
radioimmunoassay
- RP
reversed phase
- SEM
standard error of mean 相似文献
17.
H Hietter A Van Dorsselaer B Green L Denoroy J Hoffmann B Luu 《European journal of biochemistry》1990,187(1):241-247
Two predominant peptides have been isolated from neurohaemal lobes of corpora cardiaca of 8000 adults of Locusta migratoria. Both peptides have been unambiguously characterized by automated peptide microsequencing and liquid secondary-ion mass spectrometry as a 50-residue peptide (5K peptide) and a 48-residue isologue (5K' peptide). Computer search of sequence data banks did not reveal any significant similarity with other identified proteins. The 5K peptides are remarkably rich in alanine residues (25%) and contain a stretch of five consecutive alanines. This structure suggests that these molecules could correspond to spacer peptides. This assumption is corroborated in the accompanying paper [Lagueux et al. (1990) Eur. J. Biochem. 187, 249-254] on the molecular cloning of the precursor protein which attributes to the 5K peptides a role analogous to that of the C peptides of insulins. 相似文献
18.
Felix Molter Armin W. Thomas Scott A. Huettel Hauke R. Heekeren Peter N. C. Mohr 《PLoS computational biology》2022,18(7)
Choices are influenced by gaze allocation during deliberation, so that fixating an alternative longer leads to increased probability of choosing it. Gaze-dependent evidence accumulation provides a parsimonious account of choices, response times and gaze-behaviour in many simple decision scenarios. Here, we test whether this framework can also predict more complex context-dependent patterns of choice in a three-alternative risky choice task, where choices and eye movements were subject to attraction and compromise effects. Choices were best described by a gaze-dependent evidence accumulation model, where subjective values of alternatives are discounted while not fixated. Finally, we performed a systematic search over a large model space, allowing us to evaluate the relative contribution of different forms of gaze-dependence and additional mechanisms previously not considered by gaze-dependent accumulation models. Gaze-dependence remained the most important mechanism, but participants with strong attraction effects employed an additional similarity-dependent inhibition mechanism found in other models of multi-alternative multi-attribute choice. 相似文献
19.
Valter Bergant Shintaro Yamada Vincent Grass Yuta Tsukamoto Teresa Lavacca Karsten Krey MariaTeresa Mühlhofer Sabine Wittmann Armin Ensser Alexandra Herrmann Anja vom Hemdt Yuriko Tomita Shutoku Matsuyama Takatsugu Hirokawa Yiqi Huang Antonio Piras Constanze A Jakwerth Madlen Oelsner Susanne Thieme Alexander Graf Stefan Krebs Helmut Blum Beate M Kümmerer Alexey Stukalov Carsten B SchmidtWeber Manabu Igarashi Thomas Gramberg Andreas Pichlmair Hiroki Kato 《The EMBO journal》2022,41(17)
The SARS‐CoV‐2 infection cycle is a multistage process that relies on functional interactions between the host and the pathogen. Here, we repurposed antiviral drugs against both viral and host enzymes to pharmaceutically block methylation of the viral RNA 2''‐O‐ribose cap needed for viral immune escape. We find that the host cap 2''‐O‐ribose methyltransferase MTr1 can compensate for loss of viral NSP16 methyltransferase in facilitating virus replication. Concomitant inhibition of MTr1 and NSP16 efficiently suppresses SARS‐CoV‐2 replication. Using in silico target‐based drug screening, we identify a bispecific MTr1/NSP16 inhibitor with anti‐SARS‐CoV‐2 activity in vitro and in vivo but with unfavorable side effects. We further show antiviral activity of inhibitors that target independent stages of the host SAM cycle providing the methyltransferase co‐substrate. In particular, the adenosylhomocysteinase (AHCY) inhibitor DZNep is antiviral in in vitro, in ex vivo, and in a mouse infection model and synergizes with existing COVID‐19 treatments. Moreover, DZNep exhibits a strong immunomodulatory effect curbing infection‐induced hyperinflammation and reduces lung fibrosis markers ex vivo. Thus, multispecific and metabolic MTase inhibitors constitute yet unexplored treatment options against COVID‐19. 相似文献
20.