全文获取类型
收费全文 | 98610篇 |
免费 | 815篇 |
国内免费 | 888篇 |
专业分类
100313篇 |
出版年
2023年 | 15篇 |
2022年 | 63篇 |
2021年 | 98篇 |
2020年 | 83篇 |
2019年 | 112篇 |
2018年 | 11969篇 |
2017年 | 10772篇 |
2016年 | 7645篇 |
2015年 | 880篇 |
2014年 | 656篇 |
2013年 | 675篇 |
2012年 | 4750篇 |
2011年 | 13210篇 |
2010年 | 12281篇 |
2009年 | 8471篇 |
2008年 | 10140篇 |
2007年 | 11710篇 |
2006年 | 620篇 |
2005年 | 781篇 |
2004年 | 1237篇 |
2003年 | 1267篇 |
2002年 | 947篇 |
2001年 | 356篇 |
2000年 | 245篇 |
1999年 | 86篇 |
1998年 | 51篇 |
1997年 | 56篇 |
1996年 | 33篇 |
1995年 | 23篇 |
1994年 | 29篇 |
1993年 | 37篇 |
1992年 | 50篇 |
1991年 | 59篇 |
1990年 | 32篇 |
1989年 | 26篇 |
1988年 | 42篇 |
1987年 | 27篇 |
1986年 | 17篇 |
1985年 | 14篇 |
1984年 | 20篇 |
1983年 | 29篇 |
1982年 | 13篇 |
1981年 | 15篇 |
1975年 | 9篇 |
1972年 | 254篇 |
1971年 | 278篇 |
1965年 | 17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 31 毫秒
991.
Cho YS Dobos KM Prenni J Yang H Hess A Rosenkrands I Andersen P Ryoo SW Bai GH Brennan MJ Izzo A Bielefeldt-Ohmann H Belisle JT 《Proteomics》2012,12(7):979-991
Purified protein derivative (PPD) has served as a safe and effective diagnostic reagent for 60 years and is the only broadly available material to diagnose latent tuberculosis infections. This reagent is also used as a standard control for a number of in vitro immunological assays. Nevertheless, the molecular composition and specific products that contribute to the extraordinary immunological reactivity of PPD are poorly defined. Here, a proteomic approach was applied to elucidate the gene products in the U.S. Food and Drug Administration (FDA) standard PPD-S2. Many known Mycobacterium tuberculosis T-cell antigens were detected. Of significance, four heat shock proteins (HSPs) (GroES, GroEL2, HspX, and DnaK) dominated the composition of PPD. The chaperone activities and capacity of these proteins to influence immunological responses may explain the exquisite solubility and immunological potency of PPD. Spectral counting analysis of three separate PPD reagents revealed significant quantitative variances. Gross delayed-type hypersensitivity (DTH) responses in M. tuberculosis infected guinea pigs were comparable among these PPD preparations; however, detailed histopathology of the DTH lesions exposed unique differences, which may be explained by the variability observed in the presence and abundance of early secretory system (Esx) proteins. Variability in PPD reagents may explain differences in DTH responses reported among populations. 相似文献
992.
Yuki Nakamura Fumiko Yukuhiro Masaya Matsumura Hiroaki Noda 《Applied Entomology and Zoology》2012,47(3):273-283
Cytoplasmic incompatibility (CI) is a reproductive phenotype induced by bacterial endosymbionts in arthropods. Measured as a reduction in egg hatchability resulting from the crossing of uninfected females with bacteria-infected males, CI increases the frequency of bacteria-infected hosts by restricting the fertilization opportunities of uninfected hosts in populations. Wolbachia, a type of alpha-proteobacteria, is well known as a CI inducer in a wide range of arthropod species, while Cardinium, a member of the phylum Bacteroidetes, is known to cause CI in one wasp and three spider mite species. In this study, dual infection with Cardinium and Wolbachia induced strong CI in a single host, Sogatella furcifera (Horváth), a planthopper species that is naturally infected with both bacteria. Specifically, infection with Cardinium alone was found to cause a 76 % reduction in egg development, and dual infection with Cardinium and Wolbachia a 96 % reduction, indicating that Cardinium induces CI and the dual infection raises the CI level. This study was the first to document reproductive alteration by Cardinium in a diploid host species. 相似文献
993.
Il’ja Krno Ferdinand Šporka Joanna Galas Ladislav Hamerlík Zuzana Zaťovičová Peter Bitušík 《Biologia》2006,61(18):S147-S166
Littoral benthic macroinvertebrates of 45 mountain lakes in the Tatra Mountains were sampled using a semi-quantitative method in September 2000. A total of 32,852 specimens were identified to 93 taxa belonging to 14 higher taxonomic groups. Multivariate statistics (CCA, RDA) and nine biotic metrics (AQEM/STAR) were used to explain relationships between macroinvertebrate assemblages and environmental variables. Up to 57% of the ecological position of littoral macroinvertebrate assemblages were explained by variance of environmental variables divided into chemical, trophic, physical, catchment and location. Five types of Tatra lakes were recognized using CCA: A — strongly acidified lakes (small catchment, low pH, high concentration of TP, DOC, highest amount of POM in littoral); B — alpine acidified lakes (low amount of POM, low values of biotic metrics); C — alpine non-acidified lakes (high value of diversity index, predominance of Diptera); D — subalpine acidified lakes (high values of biotic metrics: number of families, proportion of crenal and rhithral taxa/total taxa); E — subalpine non-acidified lakes (high values of biotic metrics: number of families, number of genera, BMWP score, number of taxa and abundance of EPT taxa). RDA was used to design five levels of macroinvertebrate taxa acidification tolerance. The Tatra Acidification Index (TAI) was established to assess the acidification status of the lakes in the Tatra Mts. 相似文献
994.
Background
Biering-Sørenson (1984) found that individuals with less lumbar extensor muscle endurance had an increased occurrence of first episode low back pain. As a result, back endurance tests have been recommended for inclusion in health assessment protocols. However, different studies have reported markedly different values for endurance times, leading some researchers to believe that the back is receiving support from the biceps femoris and gluteus maximus. Therefore, this study was designed to examine the haemodynamic and neuromuscular activity of the erector spinae, biceps femoris, and gluteus maximus musculature during the Biering-Sørenson Muscular Endurance Test (BSME).Methods
Seventeen healthy individuals and 46 individuals with chronic low back pain performed the Biering-Sørenson Muscular Endurance Test while surface electromyography was used to quantify neuromuscular activity. Disposable silver-silver-chloride electrodes were placed in a bipolar arrangement over the right or left biceps femoris, gluteus maximus, and the lumbosacral paraspinal muscles at the level of L3. Near Infrared Spectroscopy was used simultaneously to measure tissue oxygenation and blood volume changes of the erector spinae and biceps femoris.Results
The healthy group displayed a significantly longer time to fatigue (Healthy: 168.5s, LBP: 111.1s; p ≤ 0.05). Significant differences were shown in the median frequency slope of the erector spinae between the two groups at 90–100% of the time to fatigue while no significant differences were noted in the haemodynamic data for the two groups.Conclusion
Although the BSME has been recognized as a test for back endurance, individuals with chronic LBP appear to incorporate a strategy that may help support the back musculature by utilizing the biceps femoris and gluteus maximus to a greater degree than their healthy counterparts.995.
Michael D Kennedy Mark J Haykowsky Carol A Boliek Ben TA Esch Jessica M Scott Darren ER Warburton 《Dynamic medicine : DM》2006,5(1):8
Background
Near infrared spectroscopy (NIRS) is used to assess muscle oxygenation (MO) within skeletal muscle at rest and during aerobic exercise. Previous investigations have used a single probe placement to measure MO during various forms of exercise. However, regional MO differences have been shown to exist within the same muscle which suggests that different areas of the same muscle may have divergent MO. Thus, the aim of this study was to examine whether regional differences in MO exist within the same muscle during different types of incremental (rest, 25, 50, 75, 100 % of maximum) exercise (1 leg knee extension (KE), 2 leg KE, or cycling).Methods
Nineteen healthy active males (Mean ± SD: Age 27 ± 4 yrs; VO2max: 55 ± 11 mL/kg/min) performed incremental exercise to fatigue using each mode of exercise. NIRS probes were placed on the distal and proximal portion of right leg vastus lateralis (VL). Results were analyzed with a 3-way mixed model ANOVA (probe × intensity × mode).Results
Differences in MO exist within the VL for each mode of exercise, however these differences were not consistent for each level of intensity. Comparison of MO revealed that the distal region of VL was significantly lower throughout KE exercise (1 leg KE proximal MO – distal MO = 9.9 %; 2 leg KE proximal MO – distal MO = 13 %). In contrast, the difference in MO between proximal and distal regions of VL was smaller in cycling and was not significantly different at heavy workloads (75 and 100 % of maximum).Conclusion
MO is different within the same muscle and the pattern of the difference will change depending on the mode and intensity of exercise. Future investigations should limit conclusions on MO to the area under assessment as well as the type and intensity of exercise employed.996.
Background
Allergic rhinitis (AR) and asthma are inflammatory conditions of the airways that often occur concomitantly. This global survey was undertaken to understand patient perspectives regarding symptoms, treatments, and the impact on their well-being of comorbid AR and asthma.Methods
Survey participants were adults with asthma (n = 813) and parents of children with asthma (n = 806) from four countries each in the Asia-Pacific region and Europe. Patients included in the survey also had self-reported, concomitant AR symptoms. Patients and parents were recruited by telephone interview or by direct interview.Results
Most patients (73%) had pre-existing symptoms of AR when their asthma was first diagnosed. Shortness of breath (21%) was the most troublesome symptom for adults, and wheezing (17%) and coughing (17%) the most troublesome for children. Patients used different medications for treating asthma (most commonly short-acting β-agonists and inhaled corticosteroids) and for treating AR (most commonly oral antihistamines). The concomitant presence of AR and asthma disrupted the ability to get a good night's sleep (79%), to participate in leisure and sports activities (75%), to concentrate at work or school (69% of adults, 73% of children), and to enjoy social activities (57% of adults, 51% of children). Most patients (79%) reported worsening asthma symptoms when AR symptoms flared up. Many (56%) avoided the outdoors during the allergy season because of worsening asthma symptoms. Many (60%) indicated difficulty in effectively treating both conditions, and 72% were concerned about using excessive medication. In general, respondents from the Asia-Pacific region reported more disruption of activities caused by symptoms and more concerns and difficulties with medications than did those from Europe. Differences between the two regions in medication use included more common use of inhaled corticosteroids in Europe and more common use of Chinese herbal remedies in the Asia-Pacific region.Conclusion
Results of this survey suggest that comorbid asthma and AR substantially impact patient well-being and that the worsening of AR symptoms in patients with asthma can be associated with worsening asthma symptoms. These findings underscore the need for physicians who treat patients with asthma to evaluate treatment options for improving symptoms of both AR and asthma when present concomitantly.997.
Ying Yang Zhenlong Wu Sichao Jia Sudath Dahanayaka Shuo Feng Cynthia J. Meininger Catherine J. McNeal Guoyao Wu 《Amino acids》2015,47(9):1909-1920
This study was conducted with rats to determine the safety of long-term dietary supplementation with l-arginine. Beginning at 6 weeks of age, male and female rats were fed a casein-based semi-purified diet containing 0.61 % l-arginine and received drinking water containing l-arginine-HCl (0, 1.8, or 3.6 g l-arginine/kg body-weight/day; n = 10/group). These supplemental doses of l-arginine were equivalent to 0, 286, and 573 mg l-arginine/kg body-weight/day, respectively, in humans. After a 13-week supplementation period, blood samples were obtained from rats for biochemical analyses. Supplementation with l-arginine increased plasma concentrations of arginine, ornithine, proline, homoarginine, urea, and nitric oxide metabolites without affecting those for lysine, histidine, or methylarginines, while reducing plasma concentrations of ammonia, glutamine, free fatty acids, and triglycerides. l-Arginine supplementation enhanced protein gain and reduced white-fat deposition in the body. Based on general appearance, feeding behavior, and physiological parameters, all animals showed good health during the entire experimental period; Plasma concentrations of all measured hormones (except leptin) did not differ between control and arginine-supplemented rats. l-Arginine supplementation reduced plasma levels of leptin. Additionally, l-arginine supplementation increased l-arginine:glycine amidinotransferase activity in kidneys but not in the liver or small intestine, suggesting tissue-specific regulation of enzyme expression by l-arginine. Collectively, these results indicate that dietary supplementation with l-arginine (e.g., 3.6 g/kg body-weight/day) is safe in rats for at least 91 days. This dose is equivalent to 40 g l-arginine/kg body-weight/day for a 70-kg person. Our findings help guide clinical studies to determine the safety of long-term oral administration of l-arginine to humans. 相似文献
998.
Hyaluronan lyase from Streptococcus pneumoniae can degrade hyaluronic acid, which is one of the major components in the extracellular matrix. Hyaluronan can regulate water balance, osmotic pressure, and act as an ion exchange resin. Followed by our recent work on the catalytic reaction mechanism and substrate binding mode, we in this work further investigate the functional role of active site arginine residue, R462, in the degradation of hyaluronan. The site directed mutagenesis simulation of R462A and R462Q were modeled using a combined quantum mechanical and molecular mechanical method. The overall substrate binding features upon mutations do not have significant changes. The energetic profiles for the reaction processes are essentially the same as that in wild type enzyme, but significant activation barrier height changes can be observed. Both mutants were shown to accelerate the overall enzymatic activity, e.g., R462A can reduce the barrier height by about 2.8 kcal mol–1, while R462Q reduces the activation energy by about 2.9 kcal mol–1. Consistent with the active site model calculated using density functional theory, our results can support that the positive charge on R462 guanidino side chain group plays a negative role in the catalysis. Finally, the functional role of R462 was proposed to facilitate the formation of initial enzyme-substrate complex, but not in the subsequent catalytic degradation reaction. 相似文献
999.
Marta Marcos-García Esther Menéndez Xavier Cruz-González Encarna Velázquez Pedro F. Mateos Raúl Rivas 《Symbiosis (Philadelphia, Pa.)》2015,67(1-3):11-20
The diversity of rhizobia that establish symbiosis with Lotus corniculatus has scarcely been studied. Several species of Mesorhizobium are endosymbionts of this legume, including Mesorhizobium loti, the type species of this genus. We analysed the genetic diversity of strains nodulating Lotus corniculatus in Northwest Spain and ten different RAPD patterns were identified among 22 isolates. The phylogenetic analysis of the 16S rRNA gene showed that the isolated strains belong to four divergent phylogenetic groups within the genus Mesorhizobium. These phylogenetic groups are widely distributed worldwide and the strains nodulate L. corniculatus in several countries of Europe, America and Asia. Three of the groups include the currently described Mesorhizobium species M. loti, M. erdmanii and M. jarvisii which are L. corniculatus endosymbionts. An analysis of the recA and atpD genes showed that our strains belong to several clusters, one of them very closely related to M. jarvisii and the remanining ones phylogenetically divergent from all currently described Mesorhizobium species. Some of these clusters include L. corniculatus nodulating strains isolated in Europe, America and Asia, although the recA and atpD genes have been sequenced in only a few L. corniculatus endosymbionts. The results of this study revealed great phylogenetic diversity of strains nodulating L. corniculatus, allowing us to predict that even more diversity will be discovered as further ecosystems are investigated. 相似文献
1000.
Shudipto K. Dishari Matthew R. Micklin Ki‐Joo Sung Andrew L. Zydney Adith Venkiteshwaran Jennifer N. Earley 《Biotechnology progress》2015,31(5):1280-1286
Virus filtration can provide a robust method for removal of adventitious parvoviruses in the production of biotherapeutics. Although virus filtration is typically thought to function by a purely size‐based removal mechanism, there is limited data in the literature indicating that virus retention is a function of solution conditions. The objective of this work was to examine the effect of solution pH and ionic strength on virus retention by the Viresolve® NFP membrane. Data were obtained using the bacteriophage ?X174 as a model virus, with retention data complemented by the use of confocal microscopy to directly visualize capture of fluorescently labeled ?X174 within the filter. Virus retention was greatest at low pH and low ionic strength, conditions under which there was an attractive electrostatic interaction between the negatively charged membrane and the positively charged phage. In addition, the transient increase in virus transmission seen in response to a pressure disruption at pH 7.8 and 10 was completely absent at pH 4.9, suggesting that the trapped virus are unable to overcome the electrostatic attraction and diffuse out of the pores when the pressure is released. Further confirmation of this physical picture was provided by confocal microscopy. Images obtained at pH 10 showed the migration of previously captured phage; this phenomenon was absent at pH 4.9. These results provide important new insights into the factors governing virus retention using virus filtration membranes. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:1280–1286, 2015 相似文献