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201.
David J. Aceti Craig A. Bingman Russell L. Wrobel Ronnie O. Frederick Shin-ichi Makino Karl W. Nichols Sarata C. Sahu Lai F. Bergeman Paul G. Blommel Claudia C. Cornilescu Katarzyna A. Gromek Kory D. Seder Soyoon Hwang John G. Primm Grzegorz Sabat Frank C. Vojtik Brian F. Volkman Zsolt Zolnai George N. Phillips Jr. John L. Markley Brian G. Fox 《Journal of structural and functional genomics》2015,16(2):67-80
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Muthu P Wang L Yuan CC Kazmierczak K Huang W Hernandez OM Kawai M Irving TC Szczesna-Cordary D 《FASEB journal》2011,25(12):4394-4405
The myosin essential light chain (ELC) is a structural component of the actomyosin cross-bridge, but its function is poorly understood, especially the role of the cardiac specific N-terminal extension in modulating actomyosin interaction. Here, we generated transgenic (Tg) mice expressing the A57G (alanine to glycine) mutation in the cardiac ELC known to cause familial hypertrophic cardiomyopathy (FHC). The function of the ELC N-terminal extension was investigated with the Tg-Δ43 mouse model, whose myocardium expresses a truncated ELC. Low-angle X-ray diffraction studies on papillary muscle fibers in rigor revealed a decreased interfilament spacing (≈ 1.5 nm) and no alterations in cross-bridge mass distribution in Tg-A57G mice compared to Tg-WT, expressing the full-length nonmutated ELC. The truncation mutation showed a 1.3-fold increase in I(1,1)/I(1,0), indicating a shift of cross-bridge mass from the thick filament backbone toward the thin filaments. Mechanical studies demonstrated increased stiffness in Tg-A57G muscle fibers compared to Tg-WT or Tg-Δ43. The equilibrium constant for the cross-bridge force generation step was smallest in Tg-Δ43. These results support an important role for the N-terminal ELC extension in prepositioning the cross-bridge for optimal force production. Subtle changes in the ELC sequence were sufficient to alter cross-bridge properties and lead to pathological phenotypes. 相似文献
206.
Jastrzebski K Hannan KM House CM Hung SS Pearson RB Hannan RD 《Cellular signalling》2011,23(8):1338-1347
S6K1, a critical downstream substrate of mTORC1, has been implicated in regulating protein synthesis and a variety of processes that impinge upon cell growth and proliferation. While the role of the cytoplasmic p70S6K1 isoform in the regulation of translation has been intensively studied, the targets and function of the nuclear p85S6K1 isoform remain unclear. Therefore, we carried out a phospho-proteomic screen to identify novel p85S6K1 substrates. Four novel putative p85S6K1 substrates, GRP75, CCTβ, PGK1 and RACK1, and two mTORC1 substrates, ANXA4 and PSMA6 were identified, with diverse roles in chaperone function, ribosome maturation, metabolism, vesicle trafficking and the proteasome, respectively. The chaperonin subunit CCTβ was further investigated and the site of phosphorylation mapped to serine 260, a site located in the chaperonin apical domain. Consistent with this domain being involved in folding substrate interactions, we found that phosphorylation of serine 260 modulates chaperonin folding activity. 相似文献
207.
Katarzyna Kapczyńska Piotr Stefanowicz Łukasz Jaremko Mariusz Jaremko Alicja Kluczyk Zbigniew Szewczuk 《Amino acids》2011,40(3):923-932
Protein glycation is often a cause of diabetes-associated complications. The isotopically labeled peptide-derived Amadori
products may serve as standards for quantitative determination of the glycated proteins. In this paper, we discussed various
approaches to the synthesis of Amadori products labeled selectively with stable isotopes 2H, 13C and 18O. 相似文献
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209.
Management of patients with inflammatory rheumatic disease and a history of (or even a current) malignant disease poses some
particular challenges. As direct evidence of the risk of (recurrent or de novo) malignancy in patients with a history of malignant disease is scarce, such a risk may be estimated indirectly from the principal
carcinogenicity of the respective drug to be used or (also indirectly) from cancer reactivation data from the transplant literature.
In general, cancer risk is increased in patients receiving combination immunosuppressive treatment, but the risk in patients
receiving individual drugs (with the exception of alkylating agents) remains entirely unclear. Indirect evidence supports
the intuitive concept that the risk of cancer decreases over time after a successful cancer treatment. The only two studies
in rheumatic patients with a cancer history were small and have not been able to show an increase in cancer reactivation.
The risk of reactivation also depends on the site and location of the prior malignancy. In conclusion, the decision to treat
a patient with a history of cancer immunosuppressively should be shared by the rheumatologist and the oncologist. Once the
decision is established, such patients need intensive and close monitoring. 相似文献
210.
Pietkiewicz J Bronowicka-Szydełko A Dzierzba K Danielewicz R Gamian A 《The protein journal》2011,30(3):149-158
Reactive carbonyls such as 4-hydroxy-2-nonenal (4-HNE), trans-2-nonenal (T2 N), acrolein (ACR) can react readily with nucleophilic
protein sites forming of advanced glycation end-products (AGE). In this study, the human and pig muscle-specific enolase was
used as a protein model for in vitro modification by 4-HNE, T2 N and ACR. While the human enolase interaction with reactive
α-oxoaldehyde methylglyoxal (MOG) was demonstrated previously, the effect of 4-HNE, T2 N and ACR has not been identified yet.
Altering in catalytic function were observed after the enzyme incubation with these active compounds for 1–24 h at 25, 37
and 45 °C. The inhibition degree of enolase activity occurred in following order: 4-HNE > ACR > MOG > T2 N and inactivation
of pig muscle-specific enolase was more effective relatively to human enzyme. The efficiency of AGE formation depends on time
and incubation temperature with glycating agent. More amounts of insoluble AGE were formed at 45 °C. We found that pirydoxamine
and natural dipeptide carnosine counteracted AGE formation and protected enolase against the total loss of catalytic activity.
Moreover, we demonstrated for the first time that phosphatidylserine may significantly protect enolase against decrease of
catalytic activity in spite of AGE production. 相似文献