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181.
McGahan MC Harned J Mukunnemkeril M Goralska M Fleisher L Ferrell JB 《American journal of physiology. Cell physiology》2005,288(5):C1117-C1124
Glutamate has many important physiological functions, including its role as a neurotransmitter in the retina and the central nervous system. We have made the novel observations that retinal pigment epithelial cells underlying and intimately interacting with the retina secrete glutamate and that this secretion is significantly affected by iron. In addition, iron increased secretion of glutamate in cultured lens and neuronal cells, indicating that this may be a common mechanism for the regulation of glutamate production in many cell types. The activity of the iron-dependent enzyme cytosolic aconitase (c-aconitase) is increased by iron. The conversion of citrate to isocitrate by c-aconitase is the first step in a three-step process leading to glutamate formation. In the present study, iron increased c-aconitase activity, and this increase was associated with an increase in glutamate secretion. Inhibition of c-aconitase by oxalomalate decreased glutamate secretion and completely inhibited the iron-induced increase in glutamate secretion. Derangements in both glutamate secretion and iron metabolism have been noted in neurological diseases and retinal degeneration. Our results are the first to provide a functional link between these two physiologically important substances by demonstrating a significant role for iron in the regulation of glutamate production and secretion in mammalian cells resulting from iron regulation of aconitase activity. Glutamatergic systems are found in many nonneuronal tissues. We provide the first evidence that, in addition to secreting glutamate, retinal pigment epithelial cells express the vesicular glutamate transporter VGLUT1 and that regulated vesicular release of glutamate from these cells can be inhibited by riluzole. retinal pigment epithelial cells; lens epithelial cells 相似文献
182.
John W. Huffman John Liddle Sammy G. Duncan Jr. Shu Yu Billy R. Martin Jenny L. Wiley 《Bioorganic & medicinal chemistry》1998,6(12):2383-2396
The synthesis of the 3-heptyl, and the eleven isomeric 3-methylheptyl-Δ8-tetrahydrocannabinols (3–7, R and S methyl epimers, and 8) has been carried out. The synthetic approach entailed the synthesis of substituted resorcinols, which were subjected to acid catalyzed condensation with trans-para-menthadienol to provide the Δ8-THC analogue. The 1′-, 2′- and 3′-methylheptyl analogues (3–5) are considerably more potent than Δ8-THC. The 4′-, 5′- and 6′-methylheptyl isomers (6–8) are approximately equal in potency to Δ8-THC. 相似文献
183.
Human cytomegalovirus UL103 encodes a tegument protein that is conserved across herpesvirus subgroups. Mutant viruses lacking this gene product exhibit dramatically reduced accumulation of cell-free virus progeny and poor cell-to-cell spread. Given that viral proteins and viral DNA accumulate with normal kinetics in cells infected with mutant virus, UL103 appears to function during the late phase of replication, playing a critical role in egress of capsidless dense bodies and virions. Few dense bodies were observed in the extracellular space in mutant virus-infected cells in the presence or absence of the DNA encapsidation inhibitor 2-bromo-5,6-dichloro-1-(β-d-ribofuranosyl)benzimidazole. Upon reversal of encapsidation inhibition, UL103 had a striking impact on accumulation of cell-free virus, but not on accumulation of cell-associated virus. Thus, UL103 plays a novel and important role during maturation, regulating virus particle and dense body egress from infected cells. 相似文献
184.
Dunne J Drescher B Riehle H Hadwiger P Young BD Krauter J Heidenreich O 《Oligonucleotides》2003,13(5):375-380
Transfection of mammalian cells with preformed small interfering RNAs (siRNAs) permits a transient and often specific reduction of gene expression. It is possible to rapidly examine the uptake of siRNAs by transfection with fluorescently labeled siRNAs. We examined the apparent uptake of such siRNAs by several leukemic cell lines after electroporation. We show that Cy3 and Cy5-labeled siRNAs cause a significant amount of cell fluorescence, as judged by flow cytometry. In contrast, several fluorescein-labeled siRNAs could not be detected. Nevertheless, such fluoresceinated siRNAs efficiently suppressed a leukemic target gene, demonstrating that siRNA uptake must have taken place. Therefore, for cell electroporation, fluorescein-labeled siRNAs may lead to false negative results and should not be used to examine electroporation-mediated siRNA uptake. 相似文献
185.
Guido Wassink Laura Bennet Joanne O. Davidson Jenny A. Westgate Alistair J. Gunn 《PloS one》2013,8(8)
Spontaneous antenatal hypoxia is associated with high risk of adverse outcomes, however, there is little information on neural adaptation to labor-like insults. Chronically instrumented near-term sheep fetuses (125 ± 3 days, mean ± SEM) with baseline PaO2 < 17 mmHg (hypoxic group: n = 8) or > 17 mmHg (normoxic group: n = 8) received 1-minute umbilical cord occlusions repeated every 5 minutes for a total of 4 hours, or until mean arterial blood pressure (MAP) fell below 20 mmHg for two successive occlusions. 5/8 fetuses with pre-existing hypoxia were unable to complete the full series of occlusions (vs. 0/8 normoxic fetuses). Pre-existing hypoxia was associated with progressive metabolic acidosis (nadir: pH 7.08 ± 0.04 vs. 7.33 ± 0.02, p<0.01), hypotension during occlusions (nadir: 24.7 ± 1.8 vs. 51.4 ± 3.2 mmHg, p<0.01), lower carotid blood flow during occlusions (23.6 ± 6.1 vs. 63.0 ± 4.8 mL/min, p<0.01), greater suppression of EEG activity during, between, and after occlusions (p<0.01) and slower resolution of cortical impedance, an index of cytotoxic edema. No normoxic fetuses, but 4/8 hypoxic fetuses developed seizures 148 ± 45 minutes after the start of occlusions, with a seizure burden of 26 ± 6 sec during the inter-occlusion period, and 15.1 ± 3.4 min/h in the first 6 hours of recovery. In conclusion, in fetuses with pre-existing hypoxia, repeated brief asphyxia at a rate consistent with early labor is associated with hypotension, cephalic hypoperfusion, greater EEG suppression, inter-occlusion seizures, and more sustained cytotoxic edema, consistent with early onset of neural injury. 相似文献
186.
Epigenetic control of neural stem cell fate 总被引:18,自引:0,他引:18
187.
Global change‐driven effects on dissolved organic matter composition: Implications for food webs of northern lakes 下载免费PDF全文
Irena F. Creed Ann‐Kristin Bergström Charles G. Trick Nancy B. Grimm Dag O. Hessen Jan Karlsson Karen A. Kidd Emma Kritzberg Diane M. McKnight Erika C. Freeman Oscar E. Senar Agneta Andersson Jenny Ask Martin Berggren Mehdi Cherif Reiner Giesler Erin R. Hotchkiss Pirkko Kortelainen Monica M. Palta Tobias Vrede Gesa A. Weyhenmeyer 《Global Change Biology》2018,24(8):3692-3714
Northern ecosystems are experiencing some of the most dramatic impacts of global change on Earth. Rising temperatures, hydrological intensification, changes in atmospheric acid deposition and associated acidification recovery, and changes in vegetative cover are resulting in fundamental changes in terrestrial–aquatic biogeochemical linkages. The effects of global change are readily observed in alterations in the supply of dissolved organic matter (DOM)—the messenger between terrestrial and lake ecosystems—with potentially profound effects on the structure and function of lakes. Northern terrestrial ecosystems contain substantial stores of organic matter and filter or funnel DOM, affecting the timing and magnitude of DOM delivery to surface waters. This terrestrial DOM is processed in streams, rivers, and lakes, ultimately shifting its composition, stoichiometry, and bioavailability. Here, we explore the potential consequences of these global change‐driven effects for lake food webs at northern latitudes. Notably, we provide evidence that increased allochthonous DOM supply to lakes is overwhelming increased autochthonous DOM supply that potentially results from earlier ice‐out and a longer growing season. Furthermore, we assess the potential implications of this shift for the nutritional quality of autotrophs in terms of their stoichiometry, fatty acid composition, toxin production, and methylmercury concentration, and therefore, contaminant transfer through the food web. We conclude that global change in northern regions leads not only to reduced primary productivity but also to nutritionally poorer lake food webs, with discernible consequences for the trophic web to fish and humans. 相似文献
188.
Marijuana is the most widely used illicit drug in the U.S., and marijuana use by women is on the rise. Women have been found to be more susceptible to the development of cannabinoid abuse and dependence, have more severe withdrawal symptoms, and are more likely to relapse than men. The majority of research in humans suggests that women are more likely to be affected by cannabinoids than men, with reports of enhanced and decreased performance on various tasks. In rodents, females are more sensitive than males to effects of cannabinoids on tests of antinociception, motor activity, and reinforcing efficacy. Studies on effects of cannabinoid exposure during adolescence in both humans and rodents suggest that female adolescents are more likely than male adolescents to be deleteriously affected by cannabinoids. Sex differences in response to cannabinoids appear to be due to activational and perhaps organizational effects of gonadal hormones, with estradiol identified as the hormone that contributes most to the sexually dimorphic effects of cannabinoids in adults. Many, but not all sexually dimorphic effects of exogenous cannabinoids can be attributed to a sexually dimorphic endocannabinoid system in rodents, although the same has not yet been established firmly for humans. A greater understanding of the mechanisms underlying sexually dimorphic effects of cannabinoids will facilitate development of sex-specific approaches to treat marijuana dependence and to use cannabinoid-based medications therapeutically. 相似文献
189.
Matthias Pauthner Jenny Yeung Chris Ullman Joost Bakker Thierry Wurch Janice M. Reichert 《MABS-AUSTIN》2016,8(3):617-652
The 26th Antibody Engineering & Therapeutics meeting, the annual meeting of The Antibody Society united over 800 participants from all over the world in San Diego from 6–10 December 2015. The latest innovations and advances in antibody research and development were discussed, covering a myriad of antibody-related topics by more than 100 speakers, who were carefully selected by The Antibody Society. As a prelude, attendees could join the pre-conference training course focusing, among others, on the engineering and enhancement of antibodies and antibody-like scaffolds, bispecific antibody engineering and adaptation to generate chimeric antigen receptor constructs. The main event covered 4 d of scientific sessions that included antibody effector functions, reproducibility of research and diagnostic antibodies, new developments in antibody-drug conjugates (ADCs), preclinical and clinical ADC data, new technologies and applications for bispecific antibodies, antibody therapeutics for non-cancer and orphan indications, antibodies to harness the cellular immune system, building comprehensive IgVH-gene repertoires through discovering, confirming and cataloging new germline IgVH genes, and overcoming resistance to clinical immunotherapy. The Antibody Society's special session focused on “Antibodies to watch” in 2016. Another special session put the spotlight on the limitations of the new definitions for the assignment of antibody international nonproprietary names introduced by the World Health Organization. The convention concluded with workshops on computational antibody design and on the promise and challenges of using next-generation sequencing for antibody discovery and engineering from synthetic and in vivo libraries. 相似文献
190.
JK Hom B Wang S Chetty J Giddy M Mazibuko J Allen RP Walensky E Losina KA Freedberg IV Bassett 《PloS one》2012,7(8):e43281