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131.
Pomerance M Carapau D Chantoux F Mockey M Correze C Francon J Blondeau JP 《Molecular endocrinology (Baltimore, Md.)》2003,17(11):2283-2294
132.
The goal of generalized logical analysis is to model complex biological systems, especially so-called regulatory systems,
such as genetic networks. This theory is mainly characterized by its capacity to find all the steady states of a given system
and the functional positive and negative circuits, which generate multistationarity and a cycle in the state sequence graph,
respectively. So far, this has been achieved by exhaustive enumeration, which severely limits the size of the systems that
can be analysed. In this paper, we introduce a mathematical function, called image function, which allows the calculation
of the value of the logical parameter associated with a logical variable depending on the state of the system. Thus the state
table of the system is represented analytically. We then show how all steady states can be derived as solutions to a system
of steady-state equations. Constraint programming, a recent method for solving constraint satisfaction problems, is applied
for that purpose. To illustrate the potential of our approach, we present results from computer experiments carried out on
very large randomly-generated systems (graphs) with hundreds, or even thousands, of interacting components, and show that
these systems can be solved using moderate computing time. Moreover, we illustrate the approach through two published applications,
one of which concerns the computation times of all steady states for a large genetic network. 相似文献
133.
An efficient solubilization buffer for plant proteins focused in immobilized pH gradients 总被引:2,自引:0,他引:2
The solubilization of a large array of proteins before electrophoresis itself is a very critical point for proteomic analyses. We compared the efficiency of several different solubilization buffers. From this work, we defined a very efficient solubilization buffer, including two chaotropes, two reducing agents (R2), two detergents (D2), and two kinds of carrier ampholytes in combination. This so-called R2D2 buffer (5 M urea, 2 M thiourea, 2% 3-[(3-cholamidopropyl) dimethyl-ammonio]-1-propane-sulfonate, 2% N-decyl-N,N-dimethyl-3-ammonio-1-propane-sulfonate, 20 mM dithiothreitol, 5 mM Tris(2-carboxyethyl) phosphine, 0.5% carrier ampholytes 4-6.5, 0.25% carrier ampholytes 3-10) proved to be very efficient for a large range of different samples and allowed us to obtain two-dimensional gels of high resolution and quality. 相似文献
134.
Rational design of a CD4 mimic that inhibits HIV-1 entry and exposes cryptic neutralization epitopes 总被引:5,自引:0,他引:5
Martin L Stricher F Missé D Sironi F Pugnière M Barthe P Prado-Gotor R Freulon I Magne X Roumestand C Ménez A Lusso P Veas F Vita C 《Nature biotechnology》2003,21(1):71-76
The conserved surfaces of the human immunodeficiency virus (HIV)-1 envelope involved in receptor binding represent potential targets for the development of entry inhibitors and neutralizing antibodies. Using structural information on a CD4-gp120-17b antibody complex, we have designed a 27-amino acid CD4 mimic, CD4M33, that presents optimal interactions with gp120 and binds to viral particles and diverse HIV-1 envelopes with CD4-like affinity. This mini-CD4 inhibits infection of both immortalized and primary cells by HIV-1, including primary patient isolates that are generally resistant to inhibition by soluble CD4. Furthermore, CD4M33 possesses functional properties of CD4, including the ability to unmask conserved neutralization epitopes of gp120 that are cryptic on the unbound glycoprotein. CD4M33 is a prototype of inhibitors of HIV-1 entry and, in complex with envelope proteins, a potential component of vaccine formulations, or a molecular target in phage display technology to develop broad-spectrum neutralizing antibodies. 相似文献
135.
136.
Baldin V Theis-Febvre N Benne C Froment C Cazales M Burlet-Schiltz O Ducommun B 《Biology of the cell / under the auspices of the European Cell Biology Organization》2003,95(8):547-554
Regulation of the intracellular localisation of its actors is one of the key mechanisms underlying cell cycle control. CDC25 phosphatases are activators of Cyclin-Dependent Kinases (CDK) that undergo nucleo-cytoplasmic shuttling during the cell cycle and in response to checkpoint activation. Here we report that the protein kinase PKB/Akt phosphorylates CDC25B on serine 353, resulting in a nuclear export-dependent cytoplasmic accumulation of the phosphatase. Oxidative stress activates PKB/Akt and reproduces the effect on CDC25B phosphorylation and localisation. However, inhibition of PKB/Akt activity only partially reverted the effect of oxidative stress on CDC25B localisation and mutation of serine 353 abolishes phosphorylation but only delays nuclear exclusion. These results indicate that additional mechanisms are also involved in preventing nuclear import of CDC25B. Our findings identify CDC25B as a target of PKB/Akt and provide new insight into the regulation of its localisation in response to stress-activated signalling pathways. 相似文献
137.
Improved gelatinase a selectivity by novel zinc binding groups containing galardin derivatives 总被引:1,自引:0,他引:1
Augé F Hornebeck W Decarme M Laronze JY 《Bioorganic & medicinal chemistry letters》2003,13(10):1783-1786
The synthesis of several analogues of galardin, a MMP inhibitor, are presented with their in vitro inhibitory activity against MMP-1 and MMP-2. These compounds contain a distinct Zinc Binding Group (ZBG). Those having a 2-acylated-heterocycle as well as a 2-arylamide function do not exhibit a good inhibition/selectivity against the enzymes tested. On the contrary, those that are based on a hydrazide scaffold present potent selectivity for MMP-2 versus MMP-1. 相似文献
138.
Philippe Pinton Laurent Schibler Edmond Cribiu Joel Gellin Martine Yerle 《Mammalian genome》2000,11(4):306-315
In total, 113 genes that have already been located in humans and goats were cytogenetically mapped in pigs. For this purpose,
165 gene-containing bacterial artificial chromosomes (BACs) isolated in goats were used in heterologous fluorescent in situ
hybridization on porcine chromosomes. Among them, 113 (or 69%) gave clear and specific signals, and 52 did not work in heterologous
conditions. These localizations are a significant contribution to development of the porcine gene map and also to the comparative
map for humans and pigs. They allowed us to specify the information obtained by Zoo-FISH while taking the gene order into
account; the number of conserved fragments detected for human and pig chromosomes reached 84. The average size of conserved
fragments could be estimated at 33 cM. As these genes had already been mapped in goats, the comparison was extended to ruminants.
The previous results obtained in this species, suggesting a correlation between human chromosome abnormalities and evolutionary
breakpoints, were confirmed in pigs.
Received: 22 July 1999 / Accepted: 3 December 1999 相似文献
139.
140.
Martine Coué Françoise Amariglio Domenico Maiorano Stéphane Bocquet Marcel Méchali 《Experimental cell research》1998,245(2):282
MCM proteins are molecular components of the DNA replication licensing system inXenopus.These proteins comprise a conserved family made up of six distinct members which have been found to associate in large protein complexes. We have used a combination of biochemical and cytological methods to study the association of soluble and chromatin-boundXenopusMCM proteins during the cell cycle. In interphase, soluble MCM proteins are found organized in a core salt-resistant subcomplex that includes MCM subunits which are known to have high affinity for histones. The interphasic complex is modified at mitosis and the subunit composition of the resulting mitotic subcomplexes is distinct, indicating that the stability of the MCM complex is under cell cycle control. Moreover, we provide evidence that the binding of MCM proteins to chromatin may occur in sequential steps involving the loading of distinct MCM subunits. Comparative analysis of the chromatin distribution of MCM2, 3, and 4 shows that the binding of MCM4 is distinct from that of MCM2 and 3. Altogether, these data suggest that licensing of chromatin by MCMs occurs in an ordered fashion involving discrete subcomplexes. 相似文献