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61.
Kundrotas P Georgieva P Shosheva A Christova P Alexov E 《International journal of biological macromolecules》2007,41(1):114-119
The nucleoside monophosphate kinases (NMPK) are important enzymes that control the ratio of mono- and di-phosphate nucleosides and participate in gene regulation and signal transduction in the cell. However, despite their importance only several 3D structures were experimentally determined in contrast to the wealth of sequences available for each of the NMPK families. To fill this gap we present a Web-based database containing structural models for all proteins of the five bacterial nucleoside monophosphate kinase (bNMPK) families. The models were computed by means of homology-based approach using a few experimentally determined bNMPK structures. The database also contains pK(a) values and their components calculated for the homology-based 3D models, which is a unique feature of the database. The BActerial Nucleoside MOnophosphate KInases (BANMOKI) database is freely accessible (http://www.ces.clemson.edu/compbio/banmoki) and offers an easy user-friendly interface for browsing, searching and downloading content of the database. The users can investigate, using the searching tools of the database, the properties of the bNMP kinases in respect to sequence composition, electrostatic interactions and structural differences. 相似文献
62.
Levisetti MG Suri A Petzold SJ Unanue ER 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(10):6051-6057
Several naturally occurring anti-insulin CD4 T cells were isolated from islet infiltrates of NOD mice. In accordance with the results of others, these T cells recognized the segment of the beta-chain from residues 9-23. Peptides encompassing the B:(9-23) sequence bound weakly to I-Ag7 in two main contiguous registers in which two residues at the carboxyl end, P20Gly and P21Glu, influenced binding and T cell reactivity. Naturally occurring insulin-reactive T cells exhibited differing reactivities with the carboxyl-terminal amino acids, although various single residue changes in either the flanks or the core segments affected T cell responses. The insulin peptides represent another example of a weak MHC-binding ligand that is highly immunogenic, giving rise to distinct populations of autoimmune T cells. 相似文献
63.
Calculation of pKas in RNA: on the structural origins and functional roles of protonated nucleotides
pK(a) calculations based on the Poisson-Boltzmann equation have been widely used to study proteins and, more recently, DNA. However, much less attention has been paid to the calculation of pK(a) shifts in RNA. There is accumulating evidence that protonated nucleotides can stabilize RNA structure and participate in enzyme catalysis within ribozymes. Here, we calculate the pK(a) shifts of nucleotides in RNA structures using numerical solutions to the Poisson-Boltzmann equation. We find that significant shifts are predicted for several nucleotides in two catalytic RNAs, the hairpin ribozyme and the hepatitis delta virus ribozyme, and that the shifts are likely to be related to their functions. We explore how different structural environments shift the pK(a)s of nucleotides from their solution values. RNA structures appear to use two basic strategies to shift pK(a)s: (a) the formation of compact structural motifs with structurally-conserved, electrostatic interactions; and (b) the arrangement of the phosphodiester backbone to focus negative electrostatic potential in specific regions. 相似文献
64.
Gender differences in biomechanical properties of intramural coronary resistance arteries of rats, an in vitro microarteriographic study 总被引:1,自引:0,他引:1
Matrai M Mericli M Nadasy GL Szekeres M Varbiro S Banhidy F Acs N Monos E Szekacs B 《Journal of biomechanics》2007,40(5):1024-1030
The prevalence of ischemic heart disease is lower in premenopausal females than in males of corresponding age. This should be related to gender differences in coronary functions. We tested whether biomechanical differences exist between intramural coronary resistance arteries of male and female rats. Intramural branches of the left anterior descending coronary artery (uniformly approximately 200microm in diameter) were isolated, cannulated and studied by microarteriography. Intraluminal pressure was increased from 2 to 90mmHg in steps and steady-state diameters were measured. Measurements were repeated in the presence of vasoconstrictor U46619 (10(-6)M) and the endothelial coronary vasodilator bradykinin (BK) (10(-6)M). Finally, passive diameters were recorded in calcium-free saline. A similar inner radius and a higher wall thickness (41.5+/-2.9microm vs. 31.4+/-2.7microm at 50mmHg in the passive condition, p<0.05) resulted in lower tangential wall stresses in male rats (18.9+/-1.9kPa vs. 24.9+/-2.5kPa at 50mmHg, p<0.05). Isobaric elastic modulus of vessels from male animals was significantly smaller at higher pressures. Vasoconstrictor response was significantly stronger in male than in female animals. Endothelial relaxations induced by BK were not different. This is the first demonstration that biomechanical characteristics of intramural coronary resistance arteries of a mammalian species are different in the male and female sexes. Higher wall thickness and higher vascular contractility in males are associated with similar endothelial function and larger high-pressure elasticity compared to females. These gender differences in biomechanics of coronary resistance arteries of rats may contribute to our better understanding the characteristic physiological and pathological differences in humans. 相似文献
65.
66.
Jean-Marie Burel Sébastien Besson Colin Blackburn Mark Carroll Richard K. Ferguson Helen Flynn Kenneth Gillen Roger Leigh Simon Li Dominik Lindner Melissa Linkert William J. Moore Balaji Ramalingam Emil Rozbicki Aleksandra Tarkowska Petr Walczysko Chris Allan Josh Moore Jason R. Swedlow 《Mammalian genome》2015,26(9-10):441-447
67.
Yumi Ueki Michael A Hadders Melanie B Weisser Isha Nasa Paula SoteloParrilla Lauren E Cressey Tanmay Gupta Emil P T Hertz Thomas Kruse Guillermo Montoya A Arockia Jeyaprakash Arminja Kettenbach Susanne M A Lens Jakob Nilsson 《EMBO reports》2021,22(7)
The shugoshin proteins are universal protectors of centromeric cohesin during mitosis and meiosis. The binding of human hSgo1 to the PP2A‐B56 phosphatase through a coiled‐coil (CC) region mediates cohesion protection during mitosis. Here we undertook a structure function analysis of the PP2A‐B56‐hSgo1 complex, revealing unanticipated aspects of complex formation and function. We establish that a highly conserved pocket on the B56 regulatory subunit is required for hSgo1 binding and cohesion protection during mitosis in human somatic cells. Consistent with this, we show that hSgo1 blocks the binding of PP2A‐B56 substrates containing a canonical B56 binding motif. We find that PP2A‐B56 bound to hSgo1 dephosphorylates Cdk1 sites on hSgo1 itself to modulate cohesin interactions. Collectively our work provides important insight into cohesion protection during mitosis. 相似文献
68.
Geu-Flores F Møldrup ME Böttcher C Olsen CE Scheel D Halkier BA 《The Plant cell》2011,23(6):2456-2469
The defense-related plant metabolites known as glucosinolates play important roles in agriculture, ecology, and human health. Despite an advanced biochemical understanding of the glucosinolate pathway, the source of the reduced sulfur atom in the core glucosinolate structure remains unknown. Recent evidence has pointed toward GSH, which would require further involvement of a GSH conjugate processing enzyme. In this article, we show that an Arabidopsis thaliana mutant impaired in the production of the γ-glutamyl peptidases GGP1 and GGP3 has altered glucosinolate levels and accumulates up to 10 related GSH conjugates. We also show that the double mutant is impaired in the production of camalexin and accumulates high amounts of the camalexin intermediate GS-IAN upon induction. In addition, we demonstrate that the cellular and subcellular localization of GGP1 and GGP3 matches that of known glucosinolate and camalexin enzymes. Finally, we show that the purified recombinant GGPs can metabolize at least nine of the 10 glucosinolate-related GSH conjugates as well as GS-IAN. Our results demonstrate that GSH is the sulfur donor in the biosynthesis of glucosinolates and establish an in vivo function for the only known cytosolic plant γ-glutamyl peptidases, namely, the processing of GSH conjugates in the glucosinolate and camalexin pathways. 相似文献
69.
Emil Tkadlec Lenka Lisická-Lachnitová Jan Losík Marta Heroldová 《Population Ecology》2011,53(3):495-500
Most modern population dynamics analyses of time series use simple population indices for ecological inference. These indices,
collected for many years for various agricultural pests or game animals, are generally believed not to distort systematically
feedback estimates because the assumption of linearity to population size roughly holds. To assess the relative importance
of this assumption, we examined the effect of nonlinearity in a burrow index for voles on feedback estimates obtained through
autoregressive modeling. We show that the issue of linearity is of less importance to ecological inference because the feedback
estimates are routinely obtained on a logarithmic scale. Transforming data to logs has a strong linearization effect, removing
most of the nonlinearity observed on the original scale. We conclude that the statistical tools for ecological inference,
such as autoregressive log-linear models, are sufficiently robust to the systematic error imposed by index nonlinearity and
that indices are valuable sources of ecological information even in situations when the assumed linear functional forms to
population size were not exactly validated. We suggest that for time series modelers, the issue of a large sampling variation
in small “noisy” populations is by far a more burning one than the systematic error due to index nonlinearity. 相似文献
70.
Alessandra Villa Valeria Lovato Emil Bujak Sarah Wulhfard Nadine Pasche Dario Neri 《MABS-AUSTIN》2011,3(3):264-272
Human monoclonal antibodies (mAbs) can routinely be isolated from phage display libraries against virtually any protein available in sufficient purity and quantity, but library design can influence epitope coverage on the target antigen. Here we describe the construction of a novel synthetic human antibody phage display library that incorporates hydrophilic or charged residues at position 52 of the CDR2 loop of the variable heavy chain domain, instead of the serine residue found in the corresponding germline gene. The novel library was used to isolate human mAbs to various antigens, including the alternatively-spliced EDA domain of fibronectin, a marker of tumor angiogenesis. In particular, the mAb 2H7 was proven to bind to a novel epitope on EDA, which does not overlap with the one recognized by the clinical-stage F8 antibody. F8 and 2H7 were used for the construction of chelating recombinant antibodies (CRAbs), whose tumor-targeting properties were assessed in vivo in biodistribution studies in mice bearing F9 teratocarcinoma, revealing a preferential accumulation at the tumor site.Key words: human antibody library, phage display, oncofetal fibronectin, vascular tumor targeting, scFv antibody fragments, chelating recombinant antibody (CRAb) 相似文献