全文获取类型
收费全文 | 96303篇 |
免费 | 481篇 |
国内免费 | 812篇 |
出版年
2023年 | 17篇 |
2022年 | 42篇 |
2021年 | 101篇 |
2020年 | 43篇 |
2019年 | 82篇 |
2018年 | 11916篇 |
2017年 | 10745篇 |
2016年 | 7585篇 |
2015年 | 758篇 |
2014年 | 497篇 |
2013年 | 544篇 |
2012年 | 4478篇 |
2011年 | 13083篇 |
2010年 | 12176篇 |
2009年 | 8333篇 |
2008年 | 9972篇 |
2007年 | 11522篇 |
2006年 | 417篇 |
2005年 | 694篇 |
2004年 | 1081篇 |
2003年 | 1148篇 |
2002年 | 873篇 |
2001年 | 278篇 |
2000年 | 174篇 |
1999年 | 48篇 |
1998年 | 26篇 |
1997年 | 36篇 |
1996年 | 14篇 |
1995年 | 15篇 |
1994年 | 21篇 |
1993年 | 44篇 |
1992年 | 32篇 |
1991年 | 45篇 |
1990年 | 11篇 |
1989年 | 18篇 |
1988年 | 27篇 |
1987年 | 20篇 |
1985年 | 6篇 |
1984年 | 10篇 |
1983年 | 20篇 |
1980年 | 8篇 |
1979年 | 7篇 |
1975年 | 9篇 |
1973年 | 6篇 |
1972年 | 248篇 |
1971年 | 274篇 |
1965年 | 13篇 |
1962年 | 24篇 |
1944年 | 12篇 |
1940年 | 10篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Elaine da Conceição Petronilho Magdalena do Nascimento Rennó Newton Gonçalves Castro Fernanda Motta R. da Silva Angelo da Cunha Pinto 《Journal of enzyme inhibition and medicinal chemistry》2016,31(6):1069-1078
Analogs of pralidoxime, which is a commercial antidote for intoxication from neurotoxic organophosphorus compounds, were designed, synthesized, characterized, and tested as potential inhibitors or reactivators of acetylcholinesterase (AChE) using the Ellman’s test, nuclear magnetic resonance, and molecular modeling. These analogs include 1-methylpyridine-2-carboxaldehyde hydrazone, 1-methylpyridine-2-carboxaldehyde guanylhydrazone, and six other guanylhydrazones obtained from different benzaldehydes. The results indicate that all compounds are weak AChE reactivators but relatively good AChE inhibitors. The most effective AChE inhibitor discovered was the guanylhydrazone derived from 2,4-dinitrobenzaldehyde and was compared with tacrine, displaying similar activity to this reference material. These results indicate that guanylhydrazones as well as future similar derivatives may function as drugs for the treatment of Alzheimer's disease. 相似文献
992.
M. A. Bottelier A. Schrantee G. van Wingen H. G. Ruhé M. B. de Ruiter L. Reneman 《生物学前沿》2016,11(3):256-259
Treatment of adolescents with antidepressants may induce an increased risk for suicidality in this population. The activity of the amygdala during processing of emotional faces with functional Magnetic Resonance Imaging (fMRI) is a well-known measure of emotional dysregulation. Based upon data of our prematurely ended randomized clinical trial with fluoxetine (NTR3103) in anxious and or depressed girls (12–14 years of age) we calculated that with the found effect size of r = 0.66, compared to placebo, only 8 subjects are needed to demonstrate increased amygdala activity following 16 weeks of treatment with fluoxetine. 相似文献
993.
Background
Long-term exposure to drugs of abuse causes an upregulation of the cAMP-signaling pathway in the nucleus accumbens and other forebrain regions, this common neuroadaptation is thought to underlie aspects of drug tolerance and dependence. Phosphodiesterase 4 (PDE4) is an enzyme that the selective hydrolyzes intracellular cAMP. It is expressed in several brain regions that regulate the reinforcing effects of drugs of abuse.Objective
Here, we review the current knowledge about central nervous system (CNS) distribution of PDE4 isoforms and the effects of systemic and brain-region specific inhibition of PDE4 on behavioral models of drug addiction.Methods
A systematic literature search was performed using the Pubmed.Results
Using behavioral sensitization, conditioned place preference and drug self-administration as behavioral models, a large number of studies have shown that local or systemic administration of PDE4 inhibitors reduce drug intake and/or drug seeking for psychostimulants, alcohol, and opioids in rats or mice.Conclusions
Preclinical studies suggest that PDE4 could be a therapeutic target for several classes of substance use disorder. We conclude by identifying opportunities for the development of subtype-selective PDE4 inhibitors that may reduce addiction liability and minimize the side effects that limit the clinical potential of non-selective PDE4 inhibitors. Several PDE4 inhibitors have been clinically approved for other diseases. There is a promising possibility to repurpose these PDE4 inhibitors for the treatment of drug addiction as they are safe and well-tolerated in patients.994.
995.
Hansa Jain 《生物学前沿》2016,11(5):387-390
Periodontitis is a polymicrobial disease inciting inflammatory destruction of the tooth-supporting tissues, i.e., periodontium. The initiation of this infectious disease is ascribed to the formation of subgingival biofilms. These biofilms cause stimulation of myriad of chronic inflammatory reactions by the affected tissue. The Gram-negative anaerobe Porphyromonas gingivalis is commonly found as part of the microbiota of subgingival biofilms, and is involved in the occurrence of the disease. P. gingivalis possesses numerous virulence factors supporting its survival, regulating its communication with other species in the biofilm, degrading host tissues. Fusobacterium nucleatum is pivotal for formation of biofilm and promotes growth and invasion properties of P. gingivalis. Bestatin is an aminopeptide inhibitor, produced by actinomycetes. It possesses antibacterial properties against P. gingivalis and F. nucleatum. The following review focuses on action of bestatin on the mentioned bacteria. 相似文献
996.
997.
The ability to discriminate and store similar inputs as distinct representations in memory is thought to rely on a process called pattern separation in the dentate gyrus of the hippocampus. Recent computational and empirical findings support a role for adult-born granule neurons in spatial pattern separation. We reviewed rodent studies that have manipulated both hippocampal adult neurogenesis and assessed pattern separation. The majority of studies report a supporting role of adult born neurons in pattern separation as measured at the behavioral level. However, closer evaluation of the published findings reveals variation in both pattern separation tasks and in the interpretation of behavioral performance that, taken together, suggests that the role of hippocampal adult neurogenesis in pattern separation may be less established than is currently assumed. Assessment of pattern separation at the network level through the use of immediate early gene expression, optogenetic, pharmacogenetic and/or in vivo electrophysiology studies could be instrumental in further confirming a role of adult born neurons in pattern separation further. Finally, hippocampal adult neurogenesis and pattern separation are not an exclusive pair, as evidence for hippocampal adult neurogenesis contributing to the temporal separation of events in memory, forgetting and cognitive flexibility has also been found. We conclude that whereas current empirical evidence for the involvement of hippocampal adult neurogenesis in pattern separation seems supportive, there is a need for careful interpretation of behavioral findings and an integration of the various proposed functions of adult born neurons. 相似文献
998.
Fatemeh Norozi Javad Mohammadi-asl Tina Vosoughi Mohammad Ali Jalali Far Amal Saki Malehi Najmaldin Saki 《生物学前沿》2016,11(5):404-411
Objectives
Targeted therapy of Philadelphia-positive ALL and CML patients using imatinib (IM) has caused significant changes in treatment course and has increased the survival of patients. A small group of patients show resistance to IM. Acquired mutations in tyrosine kinase domain of BCR-ABL protein are a mechanism for development of resistance. T315I is one of the most common acquired mutations in this domain, which occurs in ATP binding site and inhibits the formation of hydrogen bond with IM. The aim of this study was to evaluate the prevalence of this mutation in BCR/ABL-positive CML and ALL patients.Methods
To conduct this study, 60 BCR-ABL-positive patients (including 50 CML and 10 ALL patients) who were subject to treatment with IM were selected. After taking the samples, presence of T315I mutation was assessed using ARMS-PCR on cDNA and its polymorphism was evaluated by sequencing.Results
The results showed that among 60 patients, only three patients had T315I mutation, which was detected using ARMS technique. The three patients bearing mutation were afflicted with CML and no significant association was found between blood parameters with duration of treatment in presence of mutation.Conclusions
The mutation was found in three CML patients, which indicated lower likelihood and diagnostic value of this mutation in ALL patients. Given the negative direct sequencing results in T315I patients, it can be concluded that ARMS-PCR is a more sensitive technique when the number of cancer cells is low in patients during treatment.999.
Jan Jankowski Magdalena Kubińska Jerzy Juśkiewicz Anna Czech 《Archives of animal nutrition》2016,70(2):127-140
A total of 490 eight-week-old female Hybrid Converter turkeys (body weight 4.11 ± 0.03 kg) were divided into 5 groups with 7 replicates of 14 birds each. For 8 weeks, basal diets were supplemented with methionine (Met) at following levels (weeks 9–12/weeks 13–16 of age): Group 1 – 0.34/0.29%, Group 2 – 0.39/0.34%, Groups 3 and 4 – 0.45/0.38% and 0.51/0.41%, respectively, Group 5 – 0.58/0.47%. Only in the first feeding phase the body weight gain (BWG) was affected by Met levels with the significantly highest BWG in Group 3. No treatment effects were found for feed conversion ratio, carcass yield, carcass composition and meat colour. The blood superoxide dismutase activity was significantly highest in Groups 2 and 3. The concentrations of reduced glutathione in the liver were linearly increased (p = 0.018), whereas the ratio of reduced glutathione to oxidised glutathione was highest in Group 3 (quadratic contrast, p = 0.004). It can be concluded that turkeys from Group 3 (Met levels age depending 15% and 10% above recommendations by NRC) were characterised by a well-balanced physiological response. Attention should be paid to the immune response of birds to higher dietary Met levels: plasma IgA concentrations decreased, whereas IL-6 and TNF-α levels increased in turkeys fed diets with the highest Met content. 相似文献
1000.
Approximate parameter inference in systems biology using gradient matching: a comparative evaluation
Benn Macdonald Mu Niu Simon Rogers Maurizio Filippone Dirk Husmeier 《Biomedical engineering online》2016,15(1):80