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931.
David W. Pennington Kirana Chomkhamsri Rana Pant Marc-Andree Wolf Giovanni Bidoglio Klaus Kögler Pavel Misiga Michel Sponar Bettina Lorz Guido Sonnemann Paolo Masoni Hongtao Wang Lin Ling Carla Castanho Chen Sau Soon Maurizio Fieschi Assunta Filareto Michael Hauschild 《The International Journal of Life Cycle Assessment》2010,15(3):231-237
Introduction
The European Commission is supporting the development of the International Reference Life Cycle Data System (ILCD). This consists primarily of the ILCD Handbook and the ILCD Data Network. This paper gives an insight into the scientific positions of business, governments, consultants, academics, and others that were expressed at this public consultation workshop.Workshop focus
The workshop focused on four of the topics of the main guidance documents of the ILCD Handbook: (1) general guidance on life cycle assessment (LCA); (2) guidance for generic and average life cycle inventory (LCI) data sets; (3) requirements for environmental impact assessment methods, models and indicators for LCA; and (4) review schemes for LCA.Workshop participation
This consultation workshop was attended by more than 120 participants during the 4 days of the workshop. Representatives came from 23 countries, from both within and outside the European Union.Workshop structure
Approximately half of the participants were from business associations or individual companies. Another 20% were governmental representatives. Others came predominantly from consultancies and academia.Results
This public consultation workshop provided valuable inputs into the overall ILCD Handbook developments as well as for further development. This paper focuses on some of the main scientific issues that were raised. 相似文献932.
Mireia Martín-Satué Elise G. Lavoie Michel Fausther Joanna Lecka Elisabet Aliagas Filip Kukulski Jean Sévigny 《Histochemistry and cell biology》2010,133(6):659-668
Extracellular ATP and its hydrolysis product adenosine modulate various reproductive functions such as those requiring contraction,
steroidogenesis, and maintenance of fluid composition. Interestingly, adenosine might act as a key capacitative effector for
mammalian spermatozoa to acquire the capacity for fertilisation. Extracellular nucleotide levels are affected by cell surface
ectonucleotidases, amongst which the ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) family regroups the most abundant
and effective enzymes to hydrolyse ATP and ADP to AMP in physiological conditions. In the male reproductive tract three members
of this family have been indentified: NTPDase1, NTPDase2 and NTPDase3 (Martín-Satué et al. in Histochem Cell Biol 131:615–628,
2009). The purpose of the present study was to characterize in the male reproductive tract the expression profile of the main
enzyme responsible for the generation of adenosine from AMP, namely the ecto-5′-nucleotidase (CD73). The enzyme was identified
by immunological techniques and by in situ enzymatic assays, including inhibition experiments with α,β-methylene-ADP, a specific
CD73 inhibitor. High levels of ecto-5′-nucleotidase were detected in testes in association with both germinal and somatic
cells, in smooth muscle cells throughout the tract, in secretory epithelia from exocrine glands, and remarkably, in principal
cells of epididymis, where co-localization with NTPDase3 was found. The relevance of this co-expression on nucleotide hydrolysis
in these cells directly involved in the control of sperm fluid composition was addressed biochemically. This study suggests
close regulation of extracellular nucleoside and nucleotide levels in the genital tract by ecto-5′-nucleotidase that, in concurrence
with NTPDases, may impact male fertility. 相似文献
933.
934.
Robert J. Gleave Daryl S. Walter Paul J. Beswick Elena Fonfria Anton D. Michel Shilina A. Roman Sac-Pham Tang 《Bioorganic & medicinal chemistry letters》2010,20(16):4951-4954
A series of analogues of the pyrazole lead 1 were synthesized in which the heterocyclic core was replaced with an imidazole. A number of potent antagonists were identified and structure–activity relationships (SAR) were investigated both with respect to activity at the P2X7 receptor and in vitro metabolic stability. Compound 10 was identified as a potent P2X7 antagonist with reduced in vitro metabolism and high solubility. 相似文献
935.
936.
937.
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
938.
Gaudet MM Kirchhoff T Green T Vijai J Korn JM Guiducci C Segrè AV McGee K McGuffog L Kartsonaki C Morrison J Healey S Sinilnikova OM Stoppa-Lyonnet D Mazoyer S Gauthier-Villars M Sobol H Longy M Frenay M GEMO Study Collaborators Hogervorst FB Rookus MA Collée JM Hoogerbrugge N van Roozendaal KE;HEBON Study Collaborators Piedmonte M Rubinstein W Nerenstone S Van Le L Blank SV Caldés T de la Hoya M Nevanlinna H Aittomäki K Lazaro C Blanco I Arason A Johannsson OT Barkardottir RB Devilee P 《PLoS genetics》2010,6(10):e1001183
The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (<40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (λ) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values<10(-5) and 39 SNPs had p-values<10(-4). These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, ) and for rs311499 was 0.72 (95% CI 0.61-0.85, ). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, ). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer. 相似文献
939.
The pathogenic chytrid fungus Batrachochytrium dendrobatidis (Bd) is considered responsible for the population declines and extinctions of hundreds of amphibian species worldwide. The panzootic
was likely triggered by human-assisted spread, but once the pathogen becomes established in a given region, its distribution
is probably determined by local drivers. To assess the relative importance of potential drivers of infection in red-spotted
newts (Notophthalmus viridescens), we measured Bd levels in 16 populations throughout central Pennsylvania. Infected individuals were detected in all but four populations,
indicating that Bd is widespread in this region. We quantified local factors hypothesized to influence Bd, and found that infection levels were best predicted by the proportion of the pond substrate consisting of leaf litter or
vegetation, along with a significant effect of water temperature. Bd infection in amphibians is temperature-dependent, and one possible explanation of the apparent substrate effect is that tree
cover and vegetation provide shade, reducing the availability of shallow, warm-water patches in which newts might reduce or
clear Bd infections. Alternatively, leaf litter and emergent vegetation might increase Bd infection more directly, perhaps by providing substrates for environmental growth of the fungus. We also observed a curvilinear
relationship between Bd load and snout-vent length (a proxy for age), hinting that newts might develop acquired resistance to Bd infection. Though correlational, these results add to a growing body of evidence suggesting that environmental temperature
is an important driver of Bd infection dynamics. 相似文献
940.