全文获取类型
收费全文 | 7474篇 |
免费 | 459篇 |
国内免费 | 20篇 |
出版年
2024年 | 14篇 |
2023年 | 102篇 |
2022年 | 278篇 |
2021年 | 411篇 |
2020年 | 377篇 |
2019年 | 561篇 |
2018年 | 443篇 |
2017年 | 310篇 |
2016年 | 393篇 |
2015年 | 410篇 |
2014年 | 504篇 |
2013年 | 640篇 |
2012年 | 607篇 |
2011年 | 593篇 |
2010年 | 311篇 |
2009年 | 274篇 |
2008年 | 297篇 |
2007年 | 294篇 |
2006年 | 256篇 |
2005年 | 210篇 |
2004年 | 166篇 |
2003年 | 115篇 |
2002年 | 104篇 |
2001年 | 18篇 |
2000年 | 14篇 |
1999年 | 19篇 |
1998年 | 21篇 |
1997年 | 16篇 |
1996年 | 16篇 |
1995年 | 6篇 |
1994年 | 10篇 |
1993年 | 13篇 |
1992年 | 6篇 |
1991年 | 14篇 |
1990年 | 6篇 |
1989年 | 11篇 |
1988年 | 8篇 |
1987年 | 12篇 |
1986年 | 12篇 |
1985年 | 13篇 |
1984年 | 13篇 |
1983年 | 8篇 |
1982年 | 6篇 |
1981年 | 5篇 |
1980年 | 6篇 |
1976年 | 3篇 |
1974年 | 7篇 |
1973年 | 3篇 |
1963年 | 2篇 |
1962年 | 2篇 |
排序方式: 共有7953条查询结果,搜索用时 15 毫秒
41.
Roger S. McIntyre Mohammad Alsuwaidan Bernhard T. Baune Michael Berk Koen Demyttenaere Joseph F. Goldberg Philip Gorwood Roger Ho Siegfried Kasper Sidney H. Kennedy Josefina Ly-Uson Rodrigo B. Mansur R. Hamish McAllister-Williams James W. Murrough Charles B. Nemeroff Andrew A. Nierenberg Joshua D. Rosenblat Gerard Sanacora Alan F. Schatzberg Richard Shelton Stephen M. Stahl Madhukar H. Trivedi Eduard Vieta Maj Vinberg Nolan Williams Allan H. Young Mario Maj 《World psychiatry》2023,22(3):394-412
Treatment-resistant depression (TRD) is common and associated with multiple serious public health implications. A consensus definition of TRD with demonstrated predictive utility in terms of clinical decision-making and health outcomes does not currently exist. Instead, a plethora of definitions have been proposed, which vary significantly in their conceptual framework. The absence of a consensus definition hampers precise estimates of the prevalence of TRD, and also belies efforts to identify risk factors, prevention opportunities, and effective interventions. In addition, it results in heterogeneity in clinical practice decision-making, adversely affecting quality of care. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have adopted the most used definition of TRD (i.e., inadequate response to a minimum of two antidepressants despite adequacy of the treatment trial and adherence to treatment). It is currently estimated that at least 30% of persons with depression meet this definition. A significant percentage of persons with TRD are actually pseudo-resistant (e.g., due to inadequacy of treatment trials or non-adherence to treatment). Although multiple sociodemographic, clinical, treatment and contextual factors are known to negatively moderate response in persons with depression, very few factors are regarded as predictive of non-response across multiple modalities of treatment. Intravenous ketamine and intranasal esketamine (co-administered with an antidepressant) are established as efficacious in the management of TRD. Some second-generation antipsychotics (e.g., aripiprazole, brexpiprazole, cariprazine, quetiapine XR) are proven effective as adjunctive treatments to antidepressants in partial responders, but only the olanzapine-fluoxetine combination has been studied in FDA-defined TRD. Repetitive transcranial magnetic stimulation (TMS) is established as effective and FDA-approved for individuals with TRD, with accelerated theta-burst TMS also recently showing efficacy. Electroconvulsive therapy is regarded as an effective acute and maintenance intervention in TRD, with preliminary evidence suggesting non-inferiority to acute intravenous ketamine. Evidence for extending antidepressant trial, medication switching and combining antidepressants is mixed. Manual-based psychotherapies are not established as efficacious on their own in TRD, but offer significant symptomatic relief when added to conventional antidepressants. Digital therapeutics are under study and represent a potential future clinical vista in this population. 相似文献
42.
43.
Hamid Rashid Mohammad Najmus Saqib Abdul Aala Rajoka Muhammad Ibrahim Siddiqui Khawar Sohail 《Biotechnology Techniques》1997,11(4):245-248
A simple, sensitive, accurate and more informative assay for determining the number of modified groups during the course of carboxyl group modification is described. Monomeric carboxymethylcellulase (CMCase) from Aspergillus niger was modified by 1-ethyl-3(3-dimethylaminopropyl)carbodiimide (EDC) in the presence of glycinamide. The different time-course aliquots were subjected to non-denaturing PAGE and the gel stained for CMCase activity. The number of carboxyl groups modified are directly read from the ladder of the enzyme bands developed at given time. This method showed that after 75 min of modification reaction there were five major species of modified CMCases in which 6 to 10 carboxyls were modified. 相似文献
44.
In this paper we describe a fast and mild method based on the use of a unique cation exchanger and buffers containing ethylene glycol and salt for the purification of the myelin basic protein (MBP; MW 18.5 kDa). MBP thus purified hydrolyses catalytically p-nitrophenyl acetate. This esterase activity facilitates not only the purification of MBP but also indicates that probably it is in its native state, i.e. there is a good chance that the purified molecules are structurally and chemically identical. This is a prerequisite to obtain crystals appropriate for x-ray diffraction and other studies.Abbreviations used MBP
myelin basic protein
- MW
molecular weight
- kDa
kilo Dalton
- octyl-POE
n-octylpolydisperse oligooxyethylene
- CHAPS
3-3-cholamidopropyl dimethylammonio-1-propane-sulfonate
- CTAB
cetyltrimethylammonium bromide
- SDS
sodium dodecyl sulfate
- SDS-PAGE
polyacrylamide gel electrophoresis in the presence of SDS
- G 3707
heptaoxyethylene lauryl ether
- TWEEN-20
polyoxyethylenesorbitan-monolaurat
- EDTA
ethylenediaminetetraacetic acid
- HEPES
N-(2-hydroxyethyl)-piperazine-N-(2-ethanesulfonic acid) 相似文献
45.
46.
Nabil Elsayed Allen Hacker Mohammad Mustafa Klaus Kuehn Gerhard Schrauzer 《Biochemical and biophysical research communications》1982,104(2):564-569
The effects of reducing glutathione peroxidase activity in the lung by changing dietary selenium intake has been investigated. In animals that were exposed to room air, selenium effects were confined to glutathione peroxidase activity, whereas under conditions of oxidant stress (ozone) the decrease in glutathione peroxidase activity prevented the stimulation of the pentose phosphate cycle (assayed by measuring glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities) which has been reported to increase in response to oxidant stress. The suppression of glutathione peroxidase activity was found to depend on dietary selenium concentration. The physiological significance of this observation may be related to the process of injury and repair in the lung. 相似文献
47.
Ovipositional responses of apple maggot (AM), Rhagoletis pomonella (Walsh), females were studied in the laboratory on apples (var: Golden Delicious) treated with different rates of four protein hydrolysate baits in choice and no-choice tests. Protein hydrolysate baits at rates of 0.5 and 1% had no significant effect, but oviposition was greatly reduced at higher rates of 5 and 10%. Apple maggot females exposed to apples treated with protein hydrolysate baits at a rate of 10% made 41–71% fewer punctures and laid 41–73% fewer eggs than in untreated control. No oviposition activity was shown on apples treated with 25 and 100% Nulure®. In no-choice tests the AM females laid 75–96% fewer eggs in apples treated with 10 and 25% Nulure compared to controls and no oviposition occurred in apples treated with 100% Nulure. Apple maggot females arrived in similar numbers on apples treated with 10% Nulure and untreated apples, but only 5% of those arriving on Nulure-treated apples showed ovipositor boring with no egg deposition while 60% of females arriving on untreated apples showed ovipositor boring activity and laid an average of 2.5 eggs per apple. In another experiment, individual AM females displayed similar behavioral responses to 10% Nulure-treated apples; none of the 56 females tested on treated apples displayed ovipositor boring activity, but 59% of the females (N=56) tested on untreated apples displayed ovipositor boring within 5 min of their arrival. Ninetyeight percent of AM females stayed and fed on fruit surfaces for 5 min on Nulure-treated apples without ovipositor boring compared to only 2% on untreated apples. Of the females that arrived on untreated apples, 39% flew away within 5 min without ovipositor boring compared to only 2% of those that arrived on Nulure-treated apples. Results of these two behavioral experiments suggest that upon arrival on a protein bait-treated apple, an apparent change of behavior occurs in AM females and instead of attempting to oviposit, they attempt to feed on fruit surfaces resulting in reduced oviposition activity. These results indicate that the feeding and oviposition-related activities of AM females are probably mutually exclusive and that the feeding behavior preempts oviposition activities on host fruits treated with higher rates of protein hydrolysate baits. 相似文献
48.
An analysis of geometrical models for computing the tertiary structure of globular proteins from the primary structure is presented. The roles of initial configuration, input information on inter-residue distances and the errors in this information are delineated. It is shown that for local information like that on secondary structure, the calculated structure is very sensitive to errors and to the initial configuration. Thus, such information is far from adequate for predicting the tertiary structure. On the other hand, global information on all the inter-residue distances is quite insensitive to errors. A semi-empirical method is presented to estimate these distances and the calculated structures are given for two proteins—pancreatic trypsin inhibitor and parvalbumin. These structures have good resemblances to those determined by X-ray diffraction. A strategy for further refinement of the method is indicated. 相似文献
49.
The multiple cholinesterase activities in canine platelets have been investigated. Platelets were homogenized by rapid decompression under nitrogen, glass tube/Teflon pestle, and glycerol lysis techniques. Rapid decompression under nitrogen technique was found to be the most efficient and gentle method for cell disruption. Homogenates were subfractionated using sodium diatrizoate density gradients. Marker enzyme assays and pulse labeling experiments with 5-hydroxyl[14C] tryptamine and [125I] thrombin on prepared subcellular fractions confirmed that the soluble, plasma membrane and the granule-1 fractions were all in reasonably pure form. Furthermore, labeling of the plasma membrane with [125I] thrombin is cited as the first successful attempt at attaining significantly bound marker for this structure. Cholinesterase activity distributions measured in these fractions indicated that about 30% of the activity was present in the plasma membrane, 50% in granule-1 and 5% in soluble fractions. Kinetic data of cholinesterase activities obtained from intact platelets, plasma membrane preparations and platelet release supernatants indicated that they are strikingly similar. 相似文献
50.
Evana N. Abdulaziz Tristan A. Bell Bazlur Rashid Mina L. Heacock Tarik Begic Owen S. Skinner Mohammad A. Yaseen Luke H. Chao Vamsi K. Mootha Antonio J. Pierik Valentin Cracan 《The Journal of biological chemistry》2022,298(8)
Microaerophilic pathogens such as Giardia lamblia, Entamoeba histolytica, and Trichomonas vaginalis have robust oxygen consumption systems to detoxify oxygen and maintain intracellular redox balance. This oxygen consumption results from H2O-forming NADH oxidase (NOX) activity of two distinct flavin-containing systems: H2O-forming NOXes and multicomponent flavodiiron proteins (FDPs). Neither system is membrane bound, and both recycle NADH into oxidized NAD+ while simultaneously removing O2 from the local environment. However, little is known about the specific contributions of these systems in T. vaginalis. In this study, we use bioinformatics and biochemical analyses to show that T. vaginalis lacks a NOX–like enzyme and instead harbors three paralogous genes (FDPF1–3), each encoding a natural fusion product between the N-terminal FDP, central rubredoxin (Rb), and C-terminal NADH:Rb oxidoreductase domains. Unlike a “stand-alone” FDP that lacks Rb and oxidoreductase domains, this natural fusion protein with fully populated flavin redox centers directly accepts reducing equivalents of NADH to catalyze the four-electron reduction of oxygen to water within a single polypeptide with an extremely high turnover. Furthermore, using single-particle cryo-EM, we present structural insights into the spatial organization of the FDP core within this multidomain fusion protein. Together, these results contribute to our understanding of systems that allow protozoan parasites to maintain optimal redox balance and survive transient exposure to oxic conditions. 相似文献