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排序方式: 共有1331条查询结果,搜索用时 15 毫秒
91.
Sara Nava Marta Dossena Simona Pogliani Serena Pellegatta Carlo Antozzi Fulvio Baggi Cinzia Gellera Bianca Pollo Eugenio A. Parati Gaetano Finocchiaro Simona Frigerio 《PloS one》2012,7(12)
Immune-based treatments represent a promising new class of therapy designed to boost the immune system to specifically eradicate malignant cells. Immunotherapy may generate specific anti-tumor immune responses, and dendritic cells (DC), professional antigen-presenting cells, are widely used in experimental cancer immunotherapy. Several reports describe methods for the generation of mature, antigen-pulsed DC for clinical use. Improved quality and standardization are desirable to obtain GMP-compliant protocols. In this study we describe the generation of DC from 31 Glioblastoma (GB) patients starting from their monocytes isolated by immunomagnetic CD14 selection using the CliniMACS® device. Upon differentiation of CD14+ with IL-4 and GM-CSF, DC were induced to maturation with TNF-α, PGE2, IL-1β, and IL-6. Whole tumor lysate was obtained, for the first time, in a closed system using the semi-automated dissociator GentleMACS®. The yield of proteins improved by 130% compared to the manual dissociation method. Interestingly the Mean Fluorescence Intensity for CD83 increased significantly in DC pulsed with “new method” lysate compared to DC pulsed with “classical method” lysate. Our results indicate that immunomagnetic isolation of CD14+ monocytes using the CliniMACS® device and their pulsing with whole tumor lysate proteins is a suitable method for clinical-scale generation of high quality, functional DC under GMP-grade conditions. 相似文献
92.
Marcel Cardillo Marcel Cardillo Marcel Cardillo Marcel Cardillo Marcel Cardillo 《PLoS biology》2004,2(7):e197
Understanding why some species are at high risk of extinction, while others remain relatively safe, is central to the development of a predictive conservation science. Recent studies have shown that a species' extinction risk may be determined by two types of factors: intrinsic biological traits and exposure to external anthropogenic threats. However, little is known about the relative and interacting effects of intrinsic and external variables on extinction risk. Using phylogenetic comparative methods, we show that extinction risk in the mammal order Carnivora is predicted more strongly by biology than exposure to high-density human populations. However, biology interacts with human population density to determine extinction risk: biological traits explain 80% of variation in risk for carnivore species with high levels of exposure to human populations, compared to 45% for carnivores generally. The results suggest that biology will become a more critical determinant of risk as human populations expand. We demonstrate how a model predicting extinction risk from biology can be combined with projected human population density to identify species likely to move most rapidly towards extinction by the year 2030. African viverrid species are particularly likely to become threatened, even though most are currently considered relatively safe. We suggest that a preemptive approach to species conservation is needed to identify and protect species that may not be threatened at present but may become so in the near future. 相似文献
93.
94.
Ferdous Nafisa Kudumala Sirisha Sossi Serena Carvelli Lucia 《Neurochemical research》2020,45(6):1399-1409
Neurochemical Research - Amphetamine (AMPH) is a systemic stimulant used to treat a variety of diseases including Attention Deficit Hyperactive Disorder, narcolepsy and obesity. Previous data... 相似文献
95.
Michele Tinti Lars Kiemer Stefano Costa Martin L. Miller Francesca Sacco Jesper V. Olsen Martina Carducci Serena Paoluzi Francesca Langone Christopher T. Workman Nikolaj Blom Kazuya Machida Christopher M. Thompson Mike Schutkowski Søren Brunak Matthias Mann Bruce J. Mayer Luisa Castagnoli Gianni Cesareni 《Cell reports》2013,3(4):1293-1305
Highlights? The recognition specificity of 70 SH2 domains is probed ? Recognition specificity diverges faster than sequence ? PepspotDB is a database of protein interactions mediated by SH2 domains 相似文献
96.
Elena Serena Elisa Figallo Nina Tandon Christopher Cannizzaro Nicola Elvassore Gordana Vunjak-Novakovic 《Experimental cell research》2009,315(20):3611-3619
Exogenous electric fields have been implied in cardiac differentiation of mouse embryonic stem cells and the generation of reactive oxygen species (ROS). In this work, we explored the effects of electrical field stimulation on ROS generation and cardiogenesis in embryoid bodies (EBs) derived from human embryonic stem cells (hESC, line H13), using a custom-built electrical stimulation bioreactor. Electrical properties of the bioreactor system were characterized by electrochemical impedance spectroscopy (EIS) and analysis of electrical currents. The effects of the electrode material (stainless steel, titanium-nitride-coated titanium, titanium), length of stimulus (1 and 90 s) and age of EBs at the onset of electrical stimulation (4 and 8 days) were investigated with respect to ROS generation. The amplitude of the applied electrical field was 1 V/mm. The highest rate of ROS generation was observed for stainless steel electrodes, for signal duration of 90 s and for 4-day-old EBs. Notably, comparable ROS generation was achieved by incubation of EBs with 1 nM H2O2. Cardiac differentiation in these EBs was evidenced by spontaneous contractions, expression of troponin T and its sarcomeric organization. These results imply that electrical stimulation plays a role in cardiac differentiation of hESCs, through mechanisms associated with the intracellular generation of ROS. 相似文献
97.
98.
Nik-Zainal S Alexandrov LB Wedge DC Van Loo P Greenman CD Raine K Jones D Hinton J Marshall J Stebbings LA Menzies A Martin S Leung K Chen L Leroy C Ramakrishna M Rance R Lau KW Mudie LJ Varela I McBride DJ Bignell GR Cooke SL Shlien A Gamble J Whitmore I Maddison M Tarpey PS Davies HR Papaemmanuil E Stephens PJ McLaren S Butler AP Teague JW Jönsson G Garber JE Silver D Miron P Fatima A Boyault S Langerød A Tutt A Martens JW Aparicio SA Borg Å Salomon AV Thomas G Børresen-Dale AL Richardson AL 《Cell》2012,149(5):979-993
99.
Cardinale A Racaniello M Saladini S De Chiara G Mollinari C de Stefano MC Pocchiari M Garaci E Merlo D 《The Journal of biological chemistry》2012,287(4):2618-2631
Accumulation of DNA damage and deficiency in DNA repair potentially contribute to the progressive neuronal loss in neurodegenerative disorders, including Alzheimer disease (AD). In multicellular eukaryotes, double strand breaks (DSBs), the most lethal form of DNA damage, are mainly repaired by the nonhomologous end joining pathway, which relies on DNA-PK complex activity. Both the presence of DSBs and a decreased end joining activity have been reported in AD brains, but the molecular player causing DNA repair dysfunction is still undetermined. β-Amyloid (Aβ), a potential proximate effector of neurotoxicity in AD, might exert cytotoxic effects by reactive oxygen species generation and oxidative stress induction, which may then cause DNA damage. Here, we show that in PC12 cells sublethal concentrations of aggregated Aβ(25-35) inhibit DNA-PK kinase activity, compromising DSB repair and sensitizing cells to nonlethal oxidative injury. The inhibition of DNA-PK activity is associated with down-regulation of the catalytic subunit DNA-PK (DNA-PKcs) protein levels, caused by oxidative stress and reversed by antioxidant treatment. Moreover, we show that sublethal doses of Aβ(1-42) oligomers enter the nucleus of PC12 cells, accumulate as insoluble oligomeric species, and reduce DNA-PK kinase activity, although in the absence of oxidative stress. Overall, these findings suggest that Aβ mediates inhibition of the DNA-PK-dependent nonhomologous end joining pathway contributing to the accumulation of DSBs that, if not efficiently repaired, may lead to the neuronal loss observed in AD. 相似文献
100.
Elena Serena Elisa Cimetta Susi Zatti Tania Zaglia Monica Zagallo Gordon Keller Nicola Elvassore 《PloS one》2012,7(11)