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991.
de Carvalho F Costa ET Camargo AA Gregorio JC Masotti C Andrade VC Strauss BE Caballero OL Atanackovic D Colleoni GW 《PloS one》2011,6(11):e27707
The MAGE-C1/CT7 encodes a cancer/testis antigen (CTA), is located on the chromosomal region Xq26-27 and is highly polymorphic in humans. MAGE-C1/CT7 is frequently expressed in multiple myeloma (MM) that may be a potential target for immunotherapy in this still incurable disease. MAGEC1/CT7 expression is restricted to malignant plasma cells and it has been suggested that MAGE-C1/CT7 might play a pathogenic role in MM; however, the exact function this protein in the pathophysiology of MM is not yet understood. Our objectives were (1) to clarify the role of MAGE-C1/CT7 in the control of cellular proliferation and cell cycle in myeloma and (2) to evaluate the impact of silencing MAGE-C1/CT7 on myeloma cells treated with bortezomib. Myeloma cell line SKO-007 was transduced for stable expression of shRNA-MAGE-C1/CT7. Downregulation of MAGE-C1/CT7 was confirmed by real time quantitative PCR and western blot. Functional assays included cell proliferation, cell invasion, cell cycle analysis and apoptosis. Western blot showed a 70-80% decrease in MAGE-C1/CT7 protein expression in inhibited cells (shRNA-MAGE-C1/CT7) when compared with controls. Functional assays did not indicate a difference in cell proliferation and DNA synthesis when inhibited cells were compared with controls. However, we found a decreased percentage of cells in the G2/M phase of the cell cycle among inhibited cells, but not in the controls (p<0.05). When myeloma cells were treated with bortezomib, we observed a 48% reduction of cells in the G2/M phase among inhibited cells while controls showed 13% (empty vector) and 9% (ineffective shRNA) reduction, respectively (p<0.01). Furthermore, inhibited cells treated with bortezomib showed an increased percentage of apoptotic cells (Annexin V+/PI-) in comparison with bortezomib-treated controls (p<0.001). We found that MAGE-C1/CT7 protects SKO-007 cells against bortezomib-induced apoptosis. Therefore, we could speculate that MAGE-C1/CT7 gene therapy could be a strategy for future therapies in MM, in particular in combination with proteasome inhibitors. 相似文献
992.
de Brouwer SJ Kraaimaat FW Sweep FC Donders RT Eijsbouts A van Koulil S van Riel PL Evers AW 《PloS one》2011,6(12):e27432
Background
Stress management interventions may prove useful in preventing the detrimental effects of stress on health. This study assessed the effects of a stress management intervention on the psychophysiological response to stress in patients with rheumatoid arthritis (RA).Methods
Seventy-four patients with RA, who were randomly assigned to either a control group or a group that received short-term stress management training, performed a standardized psychosocial stress task (Trier Social Stress Test; TSST) 1 week after the stress management training and at a 9-week follow-up. Psychological and physical functioning, and the acute psychophysiological response to the stress test were assessed.Results
Patients in the intervention group showed significantly lower psychological distress levels of anxiety after the training than did the controls. While there were no between-group differences in stress-induced tension levels, and autonomic (α-amylase) or endocrine (cortisol) responses to the stress test 1 week after the intervention, levels of stress-induced tension and cortisol were significantly lower in the intervention group at the 9-week follow-up. Overall, the response to the intervention was particularly evident in a subgroup of patients with a psychological risk profile.Conclusion
A relatively short stress management intervention can improve psychological functioning and influences the psychophysiological response to stress in patients with RA, particularly those psychologically at risk. These findings might help understand how stress can affect health and the role of individual differences in stress responsiveness.Trial Registration
TrialRegister.nl NTR1193 相似文献993.
Calderón-Santiago M Mata-Granados JM Priego-Capote F Quesada-Gómez JM Luque de Castro MD 《Analytical biochemistry》2011,(1):39-45
A selective and sensitive, fully automated platform for verification and quantitative determination of target peptides in biofluids is proposed and then validated by development of a method for analysis of cathelicidin in human serum. The method is based on the on-line coupling of solid-phase extraction (SPE) and tandem mass spectrometry with direct infusion. Mass spectrometry analysis was carried out by multiple reaction monitoring using three transitions (one for quantitative analysis and two for qualitative analysis), all them confirmed by in silico fragmentation of the target peptide. Samples were prepared in the SPE workstation on a polymeric divinylbenzene resin by preconcentration, deproteinization, and cleanup, removing salts and interferences after direct injection of human serum. The analytical process required 12 min. The limits of detection and quantitation were 2.5 and 8.25 μg/L, respectively (0.20 and 0.66 pg on column). Repeatability and within-laboratory reproducibility were 2.4% and 2.7%, respectively. A dual-cartridge configuration was used to test recovery of cathelicidin in serum, resulting in 80%. Because quantitative retention in the cartridge was assessed, determination of cathelicidin was validated without using synthetic peptides labeled with stable isotopes. The hyphenated system allows full automation, thereby improving reproducibility and accuracy, as demanded by clinical analysis. 相似文献
994.
Véronique de Berardinis David Vallenet Vanina Castelli Marielle Besnard Agnès Pinet Corinne Cruaud Sumitta Samair Christophe Lechaplais Gabor Gyapay Céline Richez Maxime Durot Annett Kreimeyer François Le Fèvre Vincent Schächter Valérie Pezo Volker Döring Claude Scarpelli Claudine Médigue Georges N Cohen Philippe Marlière Marcel Salanoubat Jean Weissenbach 《Molecular systems biology》2008,4(1)
We have constructed a collection of single‐gene deletion mutants for all dispensable genes of the soil bacterium Acinetobacter baylyi ADP1. A total of 2594 deletion mutants were obtained, whereas 499 (16%) were not, and are therefore candidate essential genes for life on minimal medium. This essentiality data set is 88% consistent with the Escherichia coli data set inferred from the Keio mutant collection profiled for growth on minimal medium, while 80% of the orthologous genes described as essential in Pseudomonas aeruginosa are also essential in ADP1. Several strategies were undertaken to investigate ADP1 metabolism by (1) searching for discrepancies between our essentiality data and current metabolic knowledge, (2) comparing this essentiality data set to those from other organisms, (3) systematic phenotyping of the mutant collection on a variety of carbon sources (quinate, 2‐3 butanediol, glucose, etc.). This collection provides a new resource for the study of gene function by forward and reverse genetic approaches and constitutes a robust experimental data source for systems biology approaches. 相似文献
995.
Low birth weight has been associated with increased obesity in adulthood. It has been shown that dietary salt restriction during intrauterine life induces low birth weight and insulin resistance in adult Wistar rats. The present study had a two-fold objective: to evaluate the effects that low salt intake during pregnancy and lactation has on the amount and distribution of adipose tissue; and to determine whether the phenotypic changes in fat mass in this model are associated with alterations in the activity of the renin-angiotensin system. Maternal salt restriction was found to reduce birth weight in male and female offspring. In adulthood, the female offspring of dams fed the low-salt diet presented higher adiposity indices than those seen in the offspring of dams fed a normal-salt diet. This was attributed to the fact that adipose tissue mass (retroperitoneal but not gonadal, mesenteric or inguinal) was greater in those rats than in the offspring of dams fed a normal diet. The adult offspring of dams fed the low-salt diet, compared to those dams fed a normal-salt diet, presented the following: plasma leptin levels higher in males and lower in females; plasma renin activity higher in males but not in females; and no differences in body weight, mean arterial blood pressure or serum angiotensin-converting enzyme activity. Therefore, low salt intake during pregnancy might lead to the programming of obesity in adult female offspring. 相似文献
996.
997.
El Hajj H Papoin J Cérède O Garcia-Réguet N Soête M Dubremetz JF Lebrun M 《Eukaryotic cell》2008,7(6):1019-1028
The protozoan parasite Toxoplasma gondii is equipped with a sophisticated secretory apparatus, including three distinct exocytic organelles, named micronemes, rhoptries, and dense granules. We have dissected the requirements for targeting the microneme protein MIC3, a key component of T. gondii infection. We have shown that MIC3 is processed in a post-Golgi compartment and that the MIC3 propeptide and epidermal growth factor (EGF) modules contain microneme-targeting information. The minimal requirement for microneme delivery is defined by the propeptide plus any one of the three EGF domains. We have demonstrated that the cleavage of the propeptide, the dimerization of MIC3, and the chitin binding-like sequence, which are crucial for host cell binding and virulence, are dispensable for proper targeting. Finally, we have shown that part of MIC3 is withheld in the secretory pathway in a cell cycle-dependent manner. 相似文献
998.
999.
Codolo G Mazzi P Amedei A Del Prete G Berton G D'Elios MM de Bernard M 《Cellular microbiology》2008,10(11):2355-2363
The Helicobacter pylori neutrophil-activating protein (HP-NAP) is able in vitro to elicit IL-12 and IL-23 production via agonistic interaction with toll-like receptor 2, and to promote Th1 polarization of allergen-specific T-cell responses. This study was aimed to assess whether systemic/intraperitoneal and/or mucosal HP-NAP administration inhibited the Th2-mediated bronchial inflammation using a mouse model of allergic asthma induced by inhaled ovalbumin (OVA). Systemic HP-NAP delivery markedly reduced the lung eosinophilia in response to repeated challenge with aerosolized OVA. Likewise, the production of IL-4, IL-5 and GM-CSF was significantly lower in the bronchoalveolar lavage of animals treated with systemic HP-NAP plus OVA than that of animals treated with OVA alone. Systemic HP-NAP also significantly resulted in both reduction of total serum IgE and increase of IL-12 plasma levels. Mucosal administration of HP-NAP was equally successful as the systemic delivery in reducing eosinophilia, IgE and Th2 cytokine levels in bronchoalveolar lavage. However, no suppression of lung eosinophilia and bronchial Th2 cytokines was observed in toll-like receptor 2-knock-out mice following HP-NAP treatment. These results identify HP-NAP as a candidate for novel strategies of prevention and treatment of allergic diseases. 相似文献
1000.
Wijnhoven TJ van de Westerlo EM Smits NC Lensen JF Rops AL van der Vlag J Berden JH van den Heuvel LP van Kuppevelt TH 《Glycoconjugate journal》2008,25(2):177-185
Heparinoids are used in the clinic as anticoagulants. A specific pentasaccharide in heparinoids activates antithrombin III,
resulting in inactivation of factor Xa and–when additional saccharides are present–inactivation of factor IIa. Structural
and functional analysis of the heterogeneous heparinoids generally requires advanced equipment, is time consuming, and needs
(extensive) sample preparation. In this study, a novel and fast method for the characterization of heparinoids is introduced
based on reactivity with nine unique anti-heparin antibodies. Eight heparinoids were biochemically analyzed by electrophoresis
and their reactivity with domain-specific anti-heparin antibodies was established by ELISA. Each heparinoid displayed a distinct
immunoprofile matching its structural characteristics. The immunoprofile could also be linked to biological characteristics,
such as the anti-Xa/anti-IIa ratio, which was reflected by reactivity of the heparinoids with antibodies HS4C3 (indicative
for 3-O-sulfates) and HS4E4 (indicative for domains allowing anti-factor IIa activity). In addition, the immunoprofile could be indicative
for heparinoid-induced side-effects, such as heparin-induced thrombocytopenia, as illustrated by reactivity with antibody
NS4F5, which defines a very high sulfated domain. In conclusion, immunoprofiling provides a novel, fast, and simple methodology
for the characterization of heparinoids, and allows high-throughput screening of (new) heparinoids for defined structural
and biological characteristics. 相似文献