全文获取类型
收费全文 | 1197篇 |
免费 | 52篇 |
出版年
2023年 | 2篇 |
2022年 | 8篇 |
2021年 | 13篇 |
2020年 | 7篇 |
2019年 | 14篇 |
2018年 | 17篇 |
2017年 | 21篇 |
2016年 | 29篇 |
2015年 | 39篇 |
2014年 | 68篇 |
2013年 | 64篇 |
2012年 | 100篇 |
2011年 | 100篇 |
2010年 | 56篇 |
2009年 | 39篇 |
2008年 | 86篇 |
2007年 | 92篇 |
2006年 | 107篇 |
2005年 | 59篇 |
2004年 | 69篇 |
2003年 | 67篇 |
2002年 | 64篇 |
2001年 | 19篇 |
2000年 | 9篇 |
1999年 | 8篇 |
1998年 | 7篇 |
1997年 | 8篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1992年 | 5篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 6篇 |
1986年 | 4篇 |
1985年 | 5篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 5篇 |
1981年 | 4篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1977年 | 4篇 |
1973年 | 4篇 |
1971年 | 1篇 |
1969年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有1249条查询结果,搜索用时 609 毫秒
991.
992.
D. Sean Froese Jolanta Kopec Fiona Fitzpatrick Marion Schuller Thomas J. McCorvie Rod Chalk Tanja Plessl Victoria Fettelschoss Brian Fowler Matthias R. Baumgartner Wyatt W. Yue 《The Journal of biological chemistry》2015,290(49):29167-29177
Conversion of vitamin B12 (cobalamin, Cbl) into the cofactor forms methyl-Cbl (MeCbl) and adenosyl-Cbl (AdoCbl) is required for the function of two crucial enzymes, mitochondrial methylmalonyl-CoA mutase and cytosolic methionine synthase, respectively. The intracellular proteins MMACHC and MMADHC play important roles in processing and targeting the Cbl cofactor to its destination enzymes, and recent evidence suggests that they may interact while performing these essential trafficking functions. To better understand the molecular basis of this interaction, we have mapped the crucial protein regions required, indicate that Cbl is likely processed by MMACHC prior to interaction with MMADHC, and identify patient mutations on both proteins that interfere with complex formation, via different mechanisms. We further report the crystal structure of the MMADHC C-terminal region at 2.2 Å resolution, revealing a modified nitroreductase fold with surprising homology to MMACHC despite their poor sequence conservation. Because MMADHC demonstrates no known enzymatic activity, we propose it as the first protein known to repurpose the nitroreductase fold solely for protein-protein interaction. Using small angle x-ray scattering, we reveal the MMACHC-MMADHC complex as a 1:1 heterodimer and provide a structural model of this interaction, where the interaction region overlaps with the MMACHC-Cbl binding site. Together, our findings provide novel structural evidence and mechanistic insight into an essential biological process, whereby an intracellular “trafficking chaperone” highly specific for a trace element cofactor functions via protein-protein interaction, which is disrupted by inherited disease mutations. 相似文献
993.
994.
The atypical response regulator HP1021 controls formation of the Helicobacter pylori replication initiation complex
下载免费PDF全文
![点击此处可从《Molecular microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Rafał Donczew Łukasz Makowski Paweł Jaworski Martyna Bezulska Małgorzata Nowaczyk Jolanta Zakrzewska‐Czerwińska Anna Zawilak‐Pawlik 《Molecular microbiology》2015,95(2):297-312
The replication of a bacterial chromosome is initiated by the DnaA protein, which binds to the specific chromosomal region oriC and unwinds duplex DNA within the DNA‐unwinding element (DUE). The initiation is tightly regulated by many factors, which control either DnaA or oriC activity and ensure that the chromosome is duplicated only when the conditions favor the survival of daughter cells. The factors controlling oriC activity often belong to the protein families of two‐component systems. Here, we found that Helicobacter pylori oriC activity is controlled by HP1021, a member of the atypical response regulator family. HP1021 protein specifically interacts with H. pylori oriC at HP1021 boxes (5′‐TGTT[TA]C[TA]‐3′), which overlap with three modules important for oriC function: DnaA boxes, the hypersensitivity (hs) region and the DUE. Consequently, HP1021 binding to oriC precludes DnaA‐oriC interactions and inhibits DNA unwinding at the DUE. Thus, HP1021 constitutes a negative regulator of the H. pylori orisome assembly in vitro. Furthermore, HP1021 boxes were found upstream of at least 70 genes, including those encoding CagA and Fur proteins. We postulate that HP1021 might coordinate chromosome replication, and thus bacterial growth, with other cellular processes and conditions in the human stomach. 相似文献
995.
A micronucleus test in combination with fluorescent in situ hybridization (FISH) using telomere-, centromere-specific probes
and 5S and 25S rDNA was used for a detailed analysis of the effects of gamma ray irradiation on the root tip meristem cells
of barley, Hordeum vulgare (2n = 14). FISH with four DNA probes was used to examine the involvement of specific chromosomes or chromosome fragments in gamma
ray-induced micronuclei formation and then to explain their origin. Additionally, a comparison of the possible origin of the
micronuclei induced by physical and chemical treatment: maleic hydrazide (MH) and N-nitroso-N-methylurea (MNU) was done. The
micronuclei induced by gamma ray could originate from acentric fragments after chromosome breakage or from whole lagging chromosomes
as a result of a dysfunction of the mitotic apparatus. No micronuclei containing only centromeric signals were found. An application
of rDNA as probes allowed it to be stated that 5S rDNA–bearing chromosomes are involved in micronuclei formation more often
than NOR chromosomes. This work allowed the origin of physically- and chemically-induced micronuclei in barley cells to be
compared: the origin of micronuclei was most often from terminal fragments. FISH confirmed its usefulness in the characterization
of micronuclei content, as well as in understanding and comparing the mechanisms of the actions of mutagens applied in plant
genotoxicity. 相似文献
996.
Leippe DM Nguyen D Zhou M Good T Kirkland TA Scurria M Bernad L Ugo T Vidugiriene J Cali JJ Klaubert DH O'Brien MA 《BioTechniques》2011,51(2):105-110
A bioluminescent general protease assay was developed using a combination of five luminogenic peptide substrates. The peptide-conjugated luciferin substrates were combined with luciferase to form a homogeneous, coupled-enzyme assay. This single-reagent format minimized backgrounds, gave stable signals, and reached peak sensitivity within 30 min. The bioluminescent assay was used to detect multiple proteases representing serine, cysteine, and metalloproteinase classes. The range of proteases detected was broader and the sensitivity greater, when compared with a standard fluorescent assay based on cleavage of the whole protein substrate casein. Fifteen of twenty proteases tested had signal-to-background ratios >10 with the bioluminescent method, compared with only seven proteases with the fluorescent approach. The bioluminescent assay also achieved lower detection limits (≤100 pg) than fluorescent methods. During protein purification processes, especially for therapeutic proteins, even trace levels of contamination can impact the protein's stability and activity. This sensitive, bioluminescent, protease assay should be useful for applications in which contaminating proteases are detrimental and protein purity is essential. 相似文献
997.
Filipiak E Walczak-Jędrzejowska R Krupiński M Oszukowska E Marchlewska K Długoński J Kula K Słowikowska-Hilczer J 《Folia histochemica et cytobiologica / Polish Academy of Sciences, Polish Histochemical and Cytochemical Society》2011,49(4):685-689
The aim of this study was to assess the impact of di(n-butyl) phthalate (DBP) on the rat's prepubertal testis. Male Wistar rats were given daily subcutaneous injections with DBP (20 or 200 μg) or a vehicle from the 5th to the 15th postnatal day (pd). On the 16(th) pd, the rats were euthanized, and the testes were dissected, weighed, and paraffin embedded. The blood was collected to determine the serum levels of testosterone (T), estradiol (E) and FSH. The following parameters were assessed in the testis sections: diameter and length of seminiferous tubules (st), numbers of spermatogonia A + intermediate + B (A/In/B), preleptotene spermatocytes (PL), leptotene + zygotene + pachytene spermatocytes (L/Z/PA) and Sertoli cells per testis, percentage of st containing gonocytes or pachytene spermatocytes or lumen. An estrogenicity in vitro test was performed by means of a transgenic yeast strain expressing human estrogen receptor alpha. At both doses, DBP had no influence on testis and seminal vesicle weight, st diameter and length, number of germ and Sertoli cells per testis, percentage of st containing gonocytes or pachytene spermatocytes or lumen. DBP did not change E, T or FSH serum levels. The in vitro yeast screen showed that DBP was a weak estrogenic compound, approximately six to seven orders of magnitude less potent than 17β-estradiol. In conclusion, exposure of a rat to DBP in doses 100 or 1,000-fold higher than a Tolerable Daily Intake for humans had no effect on its testicular development. 相似文献
998.
Wolny D Lodowska J Jaworska-Kik M Kurkiewicz S Węglarz L Dzierżewicz Z 《Archives of microbiology》2011,193(1):15-21
Lipopolysaccharides also called endotoxins are an integral component of the outer membrane of Gram-negative bacteria. When
released from the bacterial surface, they interact with a host immune system, triggering excessive inflammatory response.
Lipid A is the biologically most active part of endotoxin, and its activity is modulated by the quantity, quality and arrangement
of its fatty acids. Desulfovibrio desulfuricans is sulfate-reducing, Gram-negative bacterium that is supposed to be opportunistic pathogens of humans and animals. In the
present study, chemical composition of lipid A from various strains of D. desulfuricans was analyzed by gas chromatography/mass spectrometry. It was found that the fatty acid component of the lipid A contains
dodecanoic, tetradecanoic, 3-hydroxytetradecanoic and hexadecanoic acids, and its carbohydrate core is composed of glucosamine.
The analysis of 3-acyloxyacyl residue of the lipid A revealed the presence of amide-bound 3-(dodecanoyloxy)tetradecanoic and
3-(hexadecanoyloxy)tetradecanoic acids and ester-bound 3-(tetradecanoyloxy)tetradecanoic acid. It was concluded that both
fatty acid and 3-acyloxyacyl residue profiles of the lipid A from the studied bacteria were similar to those of E. coli and S.enterica. 相似文献
999.
Janusz Kościelniak Agnieszka Ostrowska Jolanta Biesaga-Kościelniak Władysław Filek Anna Janeczko Hazem Mohamed Kalaji Katarzyna Stalmach 《Acta Physiologiae Plantarum》2011,33(6):2329-2338
The effects of mycotoxin zearalenone (ZEN) on the photochemical activity of photosystem II (PSII) in wheat and soybean leaf
discs incubated in ZEN solutions as well as the after-effects of pre-sowing soaking of seeds in solutions containing ZEN on
the photochemical activity of PSII and on the seedlings growth under salt stress (NaCl solutions were investigated). The incubation
of wheat leaf discs in ZEN solutions strongly inhibited the energy flux per cross section (CS) for absorption (ABS/CS), trapping
(TRo/CS) and electron transport (ETo/CS), while the effects of ZEN action on soybean discs were opposite and the values of
those parameters significantly increased with the increase in ZEN concentration. Incubation of seeds in a ZEN solution resulted
in an increase in photochemical efficiency of PSII in soybean seedlings, but did not induce any response of PSII in those
of wheat at medium illuminations. Only at the stronger illumination for both species did ZEN induce an increase in efficiency
of excitation energy capture by open PSII reaction centers, photochemical quenching of chlorophyll a fluorescence and quantum yield of PSII electron transport. Pre-sowing soaking of seeds in a ZEN solution decreased the photoinhibitory
injuries of PSII in wheat and soybean due to safe scattering of the excess excitation energy through an increase in energy-dependent
quenching (qE) and state transition quenching (qT). ZEN when added to NaCl solutions during the period of germination contributed
to reduction in the growth inhibition of wheat seedlings. The incubation of wheat leaf discs in ZEN solutions strongly inhibited
CS, ABS/CS, TRo/CS and ETo/CS. Possible effects of ZEN on some physiological processes in plants have been discussed especially
in the context with photochemical activity of PSII and a salt stress. 相似文献
1000.