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591.
Grønskov K Olsen JH Sand A Pedersen W Carlsen N Bak Jylling AM Lyngbye T Brøndum-Nielsen K Rosenberg T 《Human genetics》2001,109(1):11-18
Aniridia is a severe eye disease characterized by iris hypoplasia; both sporadic cases and familial cases with an autosomal dominant inheritance exist. Mutations in the PAX6 gene have been shown to be the genetic cause of the disease. Some of the sporadic cases are caused by large chromosomal deletions, some of which also include the Wilms tumor gene (WAGR syndrome), resulting in an increased risk of developing Wilms tumor. Based on the unique registration of both cancer and aniridia cases in Denmark, we have made the most accurate risk estimate to date for Wilms tumor in sporadic aniridia. We have found that patients with sporadic aniridia have a relative risk of 67 (confidence interval: 8.1-241) of developing Wilms tumor. Among patients investigated for mutations, Wilms tumor developed in only two patients out of 5 with the Wilms tumor gene (WT1) deleted. None of the patients with smaller chromosomal deletions or intragenic mutations were found to develop Wilms tumor. Our observations suggest a smaller risk for Wilms tumor than previous estimates, and that tumor development requires deletion of WT1. We report a strategy for the mutational analysis of aniridia cases resulting in the detection of mutations in 68% of sporadic cases and 89% of familial cases. We also report four novel mutations in PAX6, and furthermore, we have discovered a new alternatively spliced form of PAX6. 相似文献
592.
The dramatic increase in the mortality of lip- and oral cancers in Hungary in the last decades points to the importance of primary and secondary prevention. Stomato-oncological screening examinations belong to the latter category, and might represent useful tools in the early diagnosis and treatment of oral carcinomas and precancerous lesions. The aim of the paper is to review the methods, results and effectivity of stomato-oncological screening examinations in Hungary. Between 1962 and 2000 nine screening examinations were performed: one on a population sample, one in an industrial setting, four connected to X-ray lung-screening examinations (one with the help of a mobile unit), one on voluntary persons, one on high risk people (homeless), one in general medical practice. Among these, in the last five years, in the course of the stomato-oncological examination of 17325 individuals, oral carcinoma has been found in 0.12%, and oral precanceroses in 2.63%. Although the general dentist is obliged by law to perform a stomato-oncological examination on the patients appearing in the practice, unfortunately, about 50-to-90% of the population does not visit a dentist regularly. The regular examination of these - high risk - groups by the help of the above methods, including the help of general medical practitioners is highly recommended. 相似文献
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594.
Mészáros T Miskolczi P Ayaydin F Pettkó-Szandtner A Peres A Magyar Z Horváth GV Bakó L Fehér A Dudits D 《Plant molecular biology》2000,43(5-6):595-605
Reversible phosphorylation of proteins by kinases and phosphatases plays a key regulatory role in several eukaryotic cellular functions including the control of the division cycle. Increasing numbers of sequence and biochemical data show the involvement of cyclin-dependent kinases (CDKs) and cyclins in regulation of the cell cycle progression in higher plants. The complexity represented by different types of CDKs and cyclins in a single species such as alfalfa, indicates that multicomponent regulatory pathways control G2/M transition. A set of cdc2-related genes (cdc2Ms A, B, D and F) was expressed in G2 and M cells. Phosphorylation assays also revealed that at least three kinase complexes (Cdc2Ms A/B, D and F) were successively active in G2/M cells after synchronization. Interaction between alfalfa mitotic cyclin (Medsa;CycB2;1) and a kinase partner has been reported previously. The present yeast two-hybrid analyses showed differential interaction between defined D-type cyclins and Cdc2Ms kinases functioning in G2/M phases. Localization of Cdc2Ms F kinase to the preprophase band (PPB), the perinuclear ring in early prophase, the mitotic spindle and the phragmoplast indicated a pivotal role for this kinase in mitotic plant cells. So far limited research efforts have been devoted to the functions of phosphatases in the control of plant cell division. A homologue of dual phosphatase, cdc25, has not been cloned yet from alfalfa; however tyrosine phosphorylation was indicated in the case of Cdc2Ms A kinase and the p13suc1-bound kinase activity was increased by treatment of this complex with recombinant Drosophila Cdc25. The potential role of serine/threonine phosphatases can be concluded from inhibitor studies based on okadaic acid or endothall. Endothall elevated the kinase activity of p13suc1-bound fractions in G2-phase alfalfa cells. These biochemical data are in accordance with observed cytological abnormalities. The present overview with selected original data outlines a conclusion that emphasizes the complexity of G2/M regulatory events in flowering plants. 相似文献
595.
Factor VII requires the cleavage of an internal peptide bond and the association with tissue factor (TF) to attain its fully active factor VIIa (FVIIa) conformation. The former event alone leaves FVIIa in a zymogen-like state of relatively low specific activity. We have designed a number of FVIIa mutants with the aim of mimicking the effect of TF, that is, creating molecules with increased intrinsic (TF-independent) enzymatic activity. Based on a possible structural difference between free and TF-bound FVIIa (Pike, A. C. W., Brzozowski, A. M., Roberts, S. M., Olsen, O. H., and Persson, E. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 8925--8930), we focused on the helical region encompassing residues 307-312 and residues in its spatial vicinity. For instance, FVIIa contains Phe-374 and Leu-305, whereas a Phe/Tyr residue in the position corresponding to 374 in homologous coagulation serine proteases is accompanied by Val in the position corresponding to 305. This conceivably results in a unique orientation of this helix in FVIIa. Substitution of Val for Leu-305 in FVIIa resulted in a 3--4-fold increase in the intrinsic amidolytic and proteolytic activity as compared with wild-type FVIIa, whereas the activity in complex with soluble TF remained the same. In accordance with this, L305V-FVIIa exhibited an increased rate of inhibition as compared with wild-type FVIIa, both by d-Phe-Phe-Arg-chloromethyl ketone and antithrombin III in the presence of heparin. The increased FVIIa activity upon replacement of Leu-305 by Val may be mediated by a movement of the 307--312 helix into an orientation resembling that found in factors IXa and Xa and thrombin. The corresponding shortening of the side chain of residue 374 (Phe --> Pro) had a smaller effect (about 1.5-fold increase) on the intrinsic activity of FVIIa. Attempts to increase FVIIa activity by introducing single or multiple mutations at positions 306, 309, and 312 to stabilize the 307-312 helix failed. 相似文献
596.
Lasse K. Bak Linea F. Obel Anne B. Walls Arne Schousboe Sevan A.A. Faek Farah S. Jajo Helle S. Waagepetersen 《ASN neuro》2012,4(3)
We have previously investigated the relative roles of extracellular glucose
and lactate as fuels for glutamatergic neurons during synaptic activity. The
conclusion from these studies was that cultured glutamatergic neurons utilize
glucose rather than lactate during NMDA (N-methyl-d-aspartate)-induced
synaptic activity and that lactate alone is not able to support neurotransmitter
glutamate homoeostasis. Subsequently, a model was proposed to explain these
results at the cellular level. In brief, the intermittent rises in intracellular
Ca2+ during activation cause influx of Ca2+ into the
mitochondrial matrix thus activating the tricarboxylic acid cycle dehydrogenases.
This will lead to a lower activity of the MASH (malate–aspartate shuttle),
which in turn will result in anaerobic glycolysis and lactate production rather
than lactate utilization. In the present work, we have investigated the effect
of an ionomycin-induced increase in intracellular Ca2+ (i.e. independent
of synaptic activity) on neuronal energy metabolism employing 13C-labelled
glucose and lactate and subsequent mass spectrometric analysis of labelling
in glutamate, alanine and lactate. The results demonstrate that glucose utilization
is positively correlated with intracellular Ca2+ whereas lactate
utilization is not. This result lends further support for a significant role
of glucose in neuronal bioenergetics and that Ca2+ signalling may
control the switch between glucose and lactate utilization during synaptic
activity. Based on the results, we propose a compartmentalized CiMASH (Ca2+-induced
limitation of the MASH) model that includes intracellular compartmentation
of glucose and lactate metabolism. We define pre- and post-synaptic compartments
metabolizing glucose and glucose plus lactate respectively in which the latter
displays a positive correlation between oxidative metabolism of glucose and
Ca2+ signalling. 相似文献
597.
Dolezal P Aili M Tong J Jiang JH Marobbio CM Marobbio CM Lee SF Schuelein R Belluzzo S Binova E Mousnier A Frankel G Giannuzzi G Palmieri F Gabriel K Naderer T Hartland EL Lithgow T 《PLoS pathogens》2012,8(1):e1002459
The Mitochondrial Carrier Family (MCF) is a signature group of integral membrane proteins that transport metabolites across the mitochondrial inner membrane in eukaryotes. MCF proteins are characterized by six transmembrane segments that assemble to form a highly-selective channel for metabolite transport. We discovered a novel MCF member, termed Legionellanucleotide carrier Protein (LncP), encoded in the genome of Legionella pneumophila, the causative agent of Legionnaire's disease. LncP was secreted via the bacterial Dot/Icm type IV secretion system into macrophages and assembled in the mitochondrial inner membrane. In a yeast cellular system, LncP induced a dominant-negative phenotype that was rescued by deleting an endogenous ATP carrier. Substrate transport studies on purified LncP reconstituted in liposomes revealed that it catalyzes unidirectional transport and exchange of ATP transport across membranes, thereby supporting a role for LncP as an ATP transporter. A hidden Markov model revealed further MCF proteins in the intracellular pathogens, Legionella longbeachae and Neorickettsia sennetsu, thereby challenging the notion that MCF proteins exist exclusively in eukaryotic organisms. 相似文献
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