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131.
A plethora of RNAs with regulatory functions has been discovered in many non-pathogenic and pathogenic bacteria. In Staphylococcus aureus, recent findings show that a large variety of RNAs control target gene expression by diverse mechanisms and many of them are expressed in response to specific internal or external signals. These RNAs comprise trans-acting RNAs, which regulate gene expression through binding with mRNAs, and cis-acting regulatory regions of mRNAs. Some of them possess multiple functions and encode small but functional peptides. In this review, we will present several examples of RNAs regulating pathogenesis, antibiotic resistance, and host-pathogen interactions and will illustrate how regulatory proteins and RNAs form complex regulatory circuits to express the virulence factors in a dynamic manner. 相似文献
132.
Thommey P. Thomas Baohua Huang Ankur Desai Hong Zong Xue-min Cheng Alina Kotlyar Pascale R. Leroueil Thomas Dunham Abraham van der Spek Brent B. Ward James R. Baker 《Bioorganic & medicinal chemistry letters》2010,20(21):6250-6253
Two morphine prodrugs (‘PDA’ and ‘PDB’) were synthesized and the kinetics of esterase-mediated morphine release from these prodrugs were determined when incubated with plasma from different animal species. Morphine was rapidly released from PDA by all species plasma with the maximum reached within 5–10 min; the released morphine was biologically active as determined by an in vitro cAMP assay. The morphine was released from PDB at a slower and species-dependent rate (mouse > rat > guinea pig > human). Morphine’s release from PDB appeared to be mediated by carboxyl esterases as the release was inhibited by the carboxyl esterase inhibitor benzil. PDA nor PDB induce cytotoxicity in the neuronal cell lines SK-NSH and SH-SY5Y. The carboxyl and amino functional moieties present on the linker portions of PDA and PDB, respectively, may facilitate their conjugation to nanoparticles to tailor morphine pharmacokinetics and specific targeting. These studies suggest the potential clinical utility of these prodrugs for morphine release at desired rates by administration of their mixture at selected ratios. 相似文献
133.
Alexandre Hinzpeter Abdel Aissat Elvira Sondo Catherine Costa Nicole Arous Christine Gameiro Natacha Martin Agathe Tarze Laurence Weiss Alix de Becdelièvre Bruno Costes Michel Goossens Luis J. Galietta Emmanuelle Girodon Pascale Fanen 《PLoS genetics》2010,6(10)
Approximately 30% of alleles causing genetic disorders generate premature termination codons (PTCs), which are usually associated with severe phenotypes. However, bypassing the deleterious stop codon can lead to a mild disease outcome. Splicing at NAGNAG tandem splice sites has been reported to result in insertion or deletion (indel) of three nucleotides. We identified such a mechanism as the origin of the mild to asymptomatic phenotype observed in cystic fibrosis patients homozygous for the E831X mutation (2623G>T) in the CFTR gene. Analyses performed on nasal epithelial cell mRNA detected three distinct isoforms, a considerably more complex situation than expected for a single nucleotide substitution. Structure-function studies and in silico analyses provided the first experimental evidence of an indel of a stop codon by alternative splicing at a NAGNAG acceptor site. In addition to contributing to proteome plasticity, alternative splicing at a NAGNAG tandem site can thus remove a disease-causing UAG stop codon. This molecular study reveals a naturally occurring mechanism where the effect of either modifier genes or epigenetic factors could be suspected. This finding is of importance for genetic counseling as well as for deciding appropriate therapeutic strategies. 相似文献
134.
Vassili Valayannopoulos Coralie Haudry Valérie Serre Magalie Barth Nathalie Boddaert Jean-Baptiste Arnoux Valérie Cormier-Daire Marlène Rio Daniel Rabier Anne Vassault Arnold Munnich Jean-Paul Bonnefont Pascale de Lonlay Agnès Rötig Anne-Sophie Lebre 《Mitochondrion》2010,10(4):335-341
Deficiencies in two subunits of the succinyl-coenzyme A synthetase (SCS) have been involved in patients with encephalomyopathy and mild methylmalonic aciduria (MMA). In this study, we described three new SUCLG1 patients and performed a meta-analysis of the literature. Our report enlarges the phenotypic spectrum of SUCLG1 mutations and confirms that a characteristic metabolic profile (presence of MMA and C4-DC carnitine in urines) and basal ganglia MRI lesions are the hallmarks of SCS defects. As mitochondrial DNA depletion in muscle is not a constant finding in SUCLG1 patients, this may suggest that diagnosis should not be based on it, but also that alternative physiopathological mechanisms may be considered to explain the combined respiratory chain deficiency observed in SCS patients. 相似文献
135.
Jean‐Charles Blouzard Pedro M. Coutinho Henri‐Pierre Fierobe Bernard Henrissat Sabrina Lignon Chantal Tardif Sandrine Pagès Pascale de Philip 《Proteomics》2010,10(3):541-554
Clostridium cellulolyticum is a model mesophilic anaerobic bacterium that efficiently degrades plant cell walls. The recent genome release offers the opportunity to analyse its complete degradation system. A total of 148 putative carbohydrate‐active enzymes were identified, and their modular structures and activities were predicted. Among them, 62 dockerin‐containing proteins bear catalytic modules from numerous carbohydrate‐active enzymes' families and whose diversity reflects the chemical and structural complexity of the plant carbohydrate. The composition of the cellulosomes produced by C. cellulolyticum upon growth on different substrates (cellulose, xylan, and wheat straw) was investigated by LC MS/MS. The majority of the proteins encoded by the cip‐cel operon, essential for cellulose degradation, were detected in all cellulosome preparations. In the presence of wheat straw, the natural and most complex of the substrates studied, additional proteins predicted to be involved in hemicellulose degradation were produced. A 32‐kb gene cluster encodes the majority of these proteins, all harbouring carbohydrate‐binding module 6 or carbohydrate‐binding module 22 xylan‐binding modules along dockerins. This newly identified xyl‐doc gene cluster, specialised in hemicellulose degradation, comes in addition of the cip‐cel operon for plant cell wall degradation. Hydrolysis efficiencies determined on the different substrates corroborates the finding that cellulosome composition is adapted to the growth substrate. 相似文献
136.
The importance of sexual reproduction for clonal plant species has long been underestimated, perhaps as a consequence of the difficulty in identifying individuals, preventing the study of their population dynamics. Such is the case for Empetrum hermaphroditum, an ericaceous species, which dominates the ground vegetation of subarctic ecosystems. Despite abundant seed production, seedlings are rarely observed. Therefore, prevalent seedling recruitment on a subarctic dune system provided an opportunity to study the population dynamics and spatial pattern of the colonization phase of this species. We established a 6-ha grid on the dune systems that extended from the shoreline to the fixed dunes and mapped and measured all E. hermaphroditum individuals in the grid. Moreover, we sampled 112 individuals just outside the grid to identify any allometric relationship between the size and age of the individuals, which allowed us to reconstruct population expansion. The overall size structure suggests that the population is still expanding. In the last 50 yr, E. hermaphroditum advanced more than 200 m in the dune system. Expansion started in the 1960s simultaneously at different distances from the shoreline. Colonization did not proceed gradually from the fixed dune toward the shoreline but instead individuals established earlier in the troughs between the dunes, with an increasingly clumped spatial pattern as the population filled in with time. 相似文献
137.
Pascale Calabrese Pierre Baconnier Aicha Laouani Julie Fontecave-Jallon Pierre-Yves Guméry André Eberhard Gila Benchetrit 《Acta biotheoretica》2010,58(2-3):265-275
To study the interaction of forces that produce chest wall motion, we propose a model based on the lever system of Hillman and Finucane (J Appl Physiol 63(3):951–961, 1987) and introduce some dynamic properties of the respiratory system. The passive elements (rib cage and abdomen) are considered as elastic compartments linked to the open air via a resistive tube, an image of airways. The respiratory muscles (active) force is applied to both compartments. Parameters of the model are identified in using experimental data of airflow signal measured by pneumotachography and rib cage and abdomen signals measured by respiratory inductive plethysmography on eleven healthy volunteers in five conditions: at rest and with four level of added loads. A breath by breath analysis showed, whatever the individual and the condition are, that there are several breaths on which the airflow simulated by our model is well fitted to the airflow measured by pneumotachography as estimated by a determination coefficient R 2 ≥ 0.70. This very simple model may well represent the behaviour of the chest wall and thus may be useful to interpret the relative motion of rib cage and abdomen during quiet breathing. 相似文献
138.
Calvaruso Christophe Turpault Marie-Pierre Uroz Stéphane Leclerc Elisabeth Kies Antoine Frey-Klett Pascale 《Plant and Soil》2010,328(1-2):145-154
The role of ectomycorrhizal fungi on mineral nutrient mobilization and uptake is crucial for tree nutrition and growth in temperate forest ecosystems. By using a “mineral weathering budget” approach, this study aims to quantify the effect of the symbiosis with the ectomycorrhizal model strain Laccaria bicolor S238N on mineral weathering and tree nutrition, carrying out a column experiment with a quartz/biotite substrate. Each column was planted with one Scots pine (Pinus sylvestris L.) non-mycorrhizal or mycorrhizal with L. bicolor, with exception of the abiotic control treatment. The columns were continuously supplied with a nutrient-poor solution. A mineral weathering budget was calculated for K and Mg. The pine shoot growth was significantly increased (73%) when plants were mycorrhizal with L. bicolor. Whatever their mycorrhizal status, pines increased mineral weathering by factors 1.5 to 2.1. No difference between non-mycorrhizal and mycorrhizal pine treatments was revealed, however, mycorrhizal pines assimilated significantly more K and Mg. This suggests that in our experimental conditions, L. bicolor S238N improved shoot growth and K and Mg assimilation in Scots pine mainly by increasing the uptake of dissolved nutrients, linked to a better exploration and exploitation of the soil by the mycorrhizal roots. 相似文献
139.
During cell migration, chemoattractant-induced signaling pathways determine the direction of movement by controlling the spatiotemporal dynamics of cytoskeletal components. In this issue of Developmental Cell, Liu et?al. report that the target of rapamycin complex 2 (TORC2) controls cell polarity and chemotaxis through regulation of both F-actin and myosin II in migrating neutrophils. 相似文献
140.
Adam R. Boyko Pascale Quignon Lin Li Jeffrey J. Schoenebeck Jeremiah D. Degenhardt Kirk E. Lohmueller Keyan Zhao Abra Brisbin Heidi G. Parker Bridgett M. vonHoldt Michele Cargill Adam Auton Andy Reynolds Abdel G. Elkahloun Marta Castelhano Dana S. Mosher Nathan B. Sutter Gary S. Johnson John Novembre Melissa J. Hubisz Adam Siepel Robert K. Wayne Carlos D. Bustamante Elaine A. Ostrander 《PLoS biology》2010,8(8)
Domestic dogs exhibit tremendous phenotypic diversity, including a greater
variation in body size than any other terrestrial mammal. Here, we generate a
high density map of canine genetic variation by genotyping 915 dogs from 80
domestic dog breeds, 83 wild canids, and 10 outbred African shelter dogs across
60,968 single-nucleotide polymorphisms (SNPs). Coupling this genomic resource
with external measurements from breed standards and individuals as well as
skeletal measurements from museum specimens, we identify 51 regions of the dog
genome associated with phenotypic variation among breeds in 57 traits. The
complex traits include average breed body size and external body dimensions and
cranial, dental, and long bone shape and size with and without allometric
scaling. In contrast to the results from association mapping of quantitative
traits in humans and domesticated plants, we find that across dog breeds, a
small number of quantitative trait loci (≤3) explain the majority of
phenotypic variation for most of the traits we studied. In addition, many
genomic regions show signatures of recent selection, with most of the highly
differentiated regions being associated with breed-defining traits such as body
size, coat characteristics, and ear floppiness. Our results demonstrate the
efficacy of mapping multiple traits in the domestic dog using a database of
genotyped individuals and highlight the important role human-directed selection
has played in altering the genetic architecture of key traits in this important
species. 相似文献