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41.
Kristyn Echterling-Savage Florence D. DiGennaro Reed L. Keith Miller Sean Savage 《Journal of applied animal welfare science : JAAWS》2013,16(2):181-197
Problem behavior of companion animals poses a threat to caregivers, other targets of problem behavior (e.g., strangers, other nonhuman animals), and those animals engaging in problem behavior. This study examined the effects of an aggression reduction procedure (ARP) on dog problem behavior. After a baseline condition showing caregivers were unsuccessful in reducing dog aggression and the behaviors preceding aggression, caregivers were trained to implement a procedure to address dog problem behavior in relatively simple contexts. Generalization programming then was used to target caregiver plan implementation and dog problem behavior in more complex contexts. The ARP effectively reduced dog aggression for all dogs. A slight reduction and increased variability in dog precursor behavior was observed when the ARP was implemented. In addition, caregivers and experts rated the goals, procedures, and effects as acceptable. Implications of these findings are discussed. 相似文献
42.
Michel Camplo Philippe Faury Anne-Sophie Charvet Florence Lederer Jean-Claude Chermann Jean-Louis Kraus 《Nucleosides, nucleotides & nucleic acids》2013,32(6):631-641
Abstract The synthesis of a new analogue of 2′,3′-dideoxy-3′-thiacytidine 9 covalently linked to an N-formyl methionyl leucyl phenylalanine peptide is described. This new prodrug analogue has been tested on the one hand as activator of human polymorphonuclear leukocytes (an EC50 value of 1.8 10?5 M was determined from dose-response curve for superoxide production) and on the other hand as inhibitor of the syncitium formation caused by HIV-1 in MT4-cells (IC50 = 8.0± 0.8 μM). In so far as this new prodrug possesses these two biological properties, it represents a useful “chemical-head” capable of targeting specific receptors located on leukocytes membranes. 相似文献
43.
Florence Miller Hervé Lécuyer Olivier Join‐Lambert Sandrine Bourdoulous Stefano Marullo Xavier Nassif Mathieu Coureuil 《Cellular microbiology》2013,15(4):512-519
The brain and meningeal spaces are protected from bacterial invasion by the blood–brain barrier, formed by specialized endothelial cells and tight intercellular junctional complexes. However, once in the bloodstream, Neisseria meningitidis crosses this barrier in about 60% of the cases. This highlights the particular efficacy with which N. meningitidis targets the brain vascular cell wall. The first step of central nervous system invasion is the direct interaction between bacteria and endothelial cells. This step is mediated by the type IV pili, which induce a remodelling of the endothelial monolayer, leading to the opening of the intercellular space. In this review, strategies used by the bacteria to survive in the bloodstream, to colonize the brain vasculature and to cross the blood–brain barrier will be discussed. 相似文献
44.
Julie Blaising Pierre L. Lévy Claire Gondeau Capucine Phelip Mihayl Varbanov Elodie Teissier Florence Ruggiero Stephen J. Polyak Nicholas H. Oberlies Tijana Ivanovic Eve‐Isabelle Pécheur 《Cellular microbiology》2013,15(11):1866-1882
Hepatitis C virus (HCV) is a global health concern infecting 170 million people worldwide. Previous studies indicate that the extract from milk thistle known as silymarin and its main component silibinin inhibit HCV infection. Here we investigated the mechanism of anti‐HCV action ofsilymarin‐derived compounds at the molecular level. By using live‐cell confocal imaging, single particle tracking, transmission electron microscopy and biochemical approaches on HCV‐infected human hepatoma cells and primary hepatocytes, we show that silibinin potently inhibits HCV infection and hinders HCV entry by slowing down trafficking through clathrin‐coated pits and vesicles. Detailed analyses revealed that silibinin altered the formation of both clathrin‐coated pits and vesicles in cells and caused abnormal uptake and trafficking of transferrin, a well‐known cargo of the clathrin endocytic pathway. Silibinin also inhibited infection by other viruses that enter cells by clathrin‐mediated endocytosis including reovirus, vesicular stomatitis and influenza viruses. Our study demonstrates that silibinin inhibits HCV early steps of infection by affecting endosomal trafficking of virions. It provides new insights into the molecular mechanisms of action of silibinin against HCV entry and also suggests that silibinin is a potential broad‐spectrum antiviral therapy. 相似文献
45.
Miriam Ragle Aure Suvi-Katri Leivonen Thomas Fleischer Qian Zhu Jens Overgaard Jan Alsner Trine Tramm Riku Louhimo Grethe I Grenaker Aln?s Merja Per?l? Florence Busato Nizar Touleimat J?rg Tost Anne-Lise B?rresen-Dale Sampsa Hautaniemi Olga G Troyanskaya Ole Christian Lingj?rde Kristine Kleivi Sahlberg Vessela N Kristensen 《Genome biology》2013,14(11):R126
Background
The global effect of copy number and epigenetic alterations on miRNA expression in cancer is poorly understood. In the present study, we integrate genome-wide DNA methylation, copy number and miRNA expression and identify genetic mechanisms underlying miRNA dysregulation in breast cancer.Results
We identify 70 miRNAs whose expression was associated with alterations in copy number or methylation, or both. Among these, five miRNA families are represented. Interestingly, the members of these families are encoded on different chromosomes and are complementarily altered by gain or hypomethylation across the patients. In an independent breast cancer cohort of 123 patients, 41 of the 70 miRNAs were confirmed with respect to aberration pattern and association to expression. In vitro functional experiments were performed in breast cancer cell lines with miRNA mimics to evaluate the phenotype of the replicated miRNAs. let-7e-3p, which in tumors is found associated with hypermethylation, is shown to induce apoptosis and reduce cell viability, and low let-7e-3p expression is associated with poorer prognosis. The overexpression of three other miRNAs associated with copy number gain, miR-21-3p, miR-148b-3p and miR-151a-5p, increases proliferation of breast cancer cell lines. In addition, miR-151a-5p enhances the levels of phosphorylated AKT protein.Conclusions
Our data provide novel evidence of the mechanisms behind miRNA dysregulation in breast cancer. The study contributes to the understanding of how methylation and copy number alterations influence miRNA expression, emphasizing miRNA functionality through redundant encoding, and suggests novel miRNAs important in breast cancer. 相似文献46.
Luc Friboulet Sophie Postel-Vinay Tony Sourisseau Julien Adam Annabelle Stoclin Florence Ponsonnailles Nicolas Dorvault Frédéric Commo Patrick Saulnier Sophie Salome-Desmoulez Géraldine Pottier Fabrice André Guido Kroemer Jean Charles Soria Ken André Olaussen 《Cell cycle (Georgetown, Tex.)》2013,12(20):3298-3306
ERCC1 (excision repair cross-complementation group 1) plays essential roles in the removal of DNA intrastrand crosslinks by nucleotide excision repair, and that of DNA interstrand crosslinks by the Fanconi anemia (FA) pathway and homology-directed repair processes (HDR). The function of ERCC1 thus impacts on the DNA damage response (DDR), particularly in anticancer therapy when DNA damaging agents are employed. ERCC1 expression has been proposed as a predictive biomarker of the response to platinum-based therapy. However, the assessment of ERCC1 expression in clinical samples is complicated by the existence of 4 functionally distinct protein isoforms, which differently impact on DDR. Here, we explored the functional competence of each ERCC1 protein isoform and obtained evidence that the 202 isoform is the sole one endowed with ERCC1 activity in DNA repair pathways. The ERCC1 isoform 202 interacts with RPA, XPA, and XPF, and XPF stability requires expression of the ERCC1 202 isoform (but none of the 3 others). ERCC1-deficient non-small cell lung cancer cells show abnormal mitosis, a phenotype reminiscent of the FA phenotype that can be rescued by isoform 202 only. Finally, we could not observe any dominant-negative interaction between ERCC1 isoforms. These data suggest that the selective assessment of the ERCC1 isoform 202 in clinical samples should accurately reflect the DDR-related activity of the gene and hence constitute a useful biomarker for customizing anticancer therapies. 相似文献
47.
Karine Monceau Mariangela Arca Lisa Leprêtre Florence Mougel Olivier Bonnard Jean-Fran?ois Silvain Nevile Maher Gérard Arnold Denis Thiéry 《PloS one》2013,8(6)
Contrary to native predators, which have co-evolved with their prey, alien predators often benefit from native prey naïveté. Vespa velutina, a honeybee predator originating from Eastern China, was introduced into France just before 2004. The present study, based on video recordings of two beehives at an early stage of the invasion process, intends to analyse the alien hornet hunting behaviour on the native prey, Apis mellifera, and to understand the interaction between the activity of the predator and the prey during the day and the season. Chasing hornets spent most of their time hovering facing the hive, to catch flying honeybees returning to the hive. The predation pressure increased during the season confirming previous study based on predator trapping. The number of honeybee captures showed a maximum peak for an intermediate number of V. velutina, unrelated to honeybee activity, suggesting the occurrence of competition between hornets. The number of honeybees caught increased during midday hours while the number of hornets did not vary, suggesting an increase in their efficacy. These results suggest that the impact of V. velutina on honeybees is limited by its own biology and behaviour and did not match the pattern of activity of its prey. Also, it could have been advantageous during the invasion, limiting resource depletion and thus favouring colonisation. This lack of synchronization may also be beneficial for honeybee colonies by giving them an opportunity to increase their activity when the hornets are less effective. 相似文献
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50.
Clémentine Schilte Frédérik Staikovsky Thérèse Couderc Yoann Madec Florence Carpentier Somar Kassab Matthew L. Albert Marc Lecuit Alain Michault 《PLoS neglected tropical diseases》2013,7(3)