全文获取类型
收费全文 | 2045篇 |
免费 | 155篇 |
国内免费 | 3篇 |
专业分类
2203篇 |
出版年
2024年 | 2篇 |
2023年 | 26篇 |
2022年 | 28篇 |
2021年 | 61篇 |
2020年 | 30篇 |
2019年 | 47篇 |
2018年 | 66篇 |
2017年 | 51篇 |
2016年 | 81篇 |
2015年 | 89篇 |
2014年 | 121篇 |
2013年 | 165篇 |
2012年 | 179篇 |
2011年 | 158篇 |
2010年 | 103篇 |
2009年 | 94篇 |
2008年 | 125篇 |
2007年 | 123篇 |
2006年 | 106篇 |
2005年 | 72篇 |
2004年 | 71篇 |
2003年 | 71篇 |
2002年 | 64篇 |
2001年 | 30篇 |
2000年 | 34篇 |
1999年 | 32篇 |
1998年 | 16篇 |
1997年 | 11篇 |
1996年 | 8篇 |
1995年 | 6篇 |
1994年 | 5篇 |
1993年 | 2篇 |
1992年 | 15篇 |
1991年 | 16篇 |
1990年 | 11篇 |
1989年 | 6篇 |
1988年 | 7篇 |
1987年 | 7篇 |
1986年 | 6篇 |
1985年 | 11篇 |
1984年 | 8篇 |
1983年 | 3篇 |
1982年 | 6篇 |
1981年 | 4篇 |
1980年 | 2篇 |
1979年 | 4篇 |
1978年 | 2篇 |
1976年 | 2篇 |
1975年 | 4篇 |
1974年 | 4篇 |
排序方式: 共有2203条查询结果,搜索用时 15 毫秒
101.
Seo-Jung Han Jae Eun Jung Do Hee Oh Minsup Kim Jae-Min Kim Kyung-Sook Chung Hee-Soo Han Jeong-Hun Lee Kyung-Tae Lee Hee Jin Jeong In Ho Park Eunkyeong Jeon Jeon-Soo Shin Dongkeun Hwang Art E. Cho Duck-Hyung Lee Taebo Sim 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):1257
Identification of highly selective type II kinase inhibitors is described. Two different chiral peptidomimetic scaffolds were introduced on the tail region of non-selective type II kinase inhibitor GNF-7 to enhance the selectivity. Kinome-wide selectivity profiling analysis showed that type II kinase inhibitor 7a potently inhibited Lck kinase with great selectivity (IC50 of 23.0 nM). It was found that 7a and its derivatives possessed high selectivity for Lck over even structurally conserved all Src family kinases. We also observed that 7a inhibited Lck activation in Jurkat T cells. Moreover, 7a was found to alleviate clinical symptoms in DSS-induced colitis mice. This study provides a novel insight into the design of selective type II kinase inhibitors by adopting chiral peptidomimetic moieties on the tail region. 相似文献
102.
Claudia T Guimaraes Christiano C Simoes Maria Marta Pastina Lyza G Maron Jurandir V Magalhaes Renato CC Vasconcellos Lauro JM Guimaraes Ubiraci GP Lana Carlos FS Tinoco Roberto W Noda Silvia N Jardim-Belicuas Leon V Kochian Vera MC Alves Sidney N Parentoni 《BMC genomics》2014,15(1)
Background
Aluminum (Al) toxicity is an important limitation to food security in tropical and subtropical regions. High Al saturation on acid soils limits root development, reducing water and nutrient uptake. In addition to naturally occurring acid soils, agricultural practices may decrease soil pH, leading to yield losses due to Al toxicity. Elucidating the genetic and molecular mechanisms underlying maize Al tolerance is expected to accelerate the development of Al-tolerant cultivars.Results
Five genomic regions were significantly associated with Al tolerance, using 54,455 SNP markers in a recombinant inbred line population derived from Cateto Al237. Candidate genes co-localized with Al tolerance QTLs were further investigated. Near-isogenic lines (NILs) developed for ZmMATE2 were as Al-sensitive as the recurrent line, indicating that this candidate gene was not responsible for the Al tolerance QTL on chromosome 5, qALT5. However, ZmNrat1, a maize homolog to OsNrat1, which encodes an Al3+ specific transporter previously implicated in rice Al tolerance, was mapped at ~40 Mbp from qALT5. We demonstrate for the first time that ZmNrat1 is preferentially expressed in maize root tips and is up-regulated by Al, similarly to OsNrat1 in rice, suggesting a role of this gene in maize Al tolerance. The strongest-effect QTL was mapped on chromosome 6 (qALT6), within a 0.5 Mbp region where three copies of the Al tolerance gene, ZmMATE1, were found in tandem configuration. qALT6 was shown to increase Al tolerance in maize; the qALT6-NILs carrying three copies of ZmMATE1 exhibited a two-fold increase in Al tolerance, and higher expression of ZmMATE1 compared to the Al sensitive recurrent parent. Interestingly, a new source of Al tolerance via ZmMATE1 was identified in a Brazilian elite line that showed high expression of ZmMATE1 but carries a single copy of ZmMATE1.Conclusions
High ZmMATE1 expression, controlled either by three copies of the target gene or by an unknown molecular mechanism, is responsible for Al tolerance mediated by qALT6. As Al tolerant alleles at qALT6 are rare in maize, marker-assisted introgression of this QTL is an important strategy to improve maize adaptation to acid soils worldwide.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-153) contains supplementary material, which is available to authorized users. 相似文献103.
Natural antibody--complement dependent neutralization of bovine herpesvirus 4 by human serum 总被引:1,自引:0,他引:1
Machiels B Gillet L Nascimento Brito SD Drion P Delforge C Nizet Y Gianello P Bona C Costes B Markine-Goriaynoff N Vanderplasschen A 《Microbes and infection / Institut Pasteur》2007,9(14-15):1530-1537
In contrast to most gammaherpesviruses, Bovine herpesvirus 4 (BoHV-4) has a broad range of host species both in vitro and in vivo. Several in vitro studies demonstrated that some human cell lines are sensitive or even permissive to BoHV-4. These observations led to the hypothesis that cross-species transmission of BoHV-4 could lead to human infections. In the present study, we investigate the sensitivity of BoHV-4 to neutralization by na?ve human sera in order to determine if humans exhibit innate anti-viral activities against this virus. Our results demonstrate that human sera from na?ve individuals, in contrast to the sera of na?ve subjects from various animal species, neutralize BoHV-4 efficiently. A series of complementary experiments were performed to unravel the mechanism(s) of this neutralization. The data obtained in this study demonstrates that human serum neutralizes BoHV-4 in a complement dependent manner activated by natural antibodies raised against the Galalpha1-3Galbeta1-4GlcNAc-R epitope expressed by bovine cells. 相似文献
104.
Reject water treatment by improvement of whole cell anammox entrapment using polyvinyl alcohol/alginate gel 总被引:1,自引:0,他引:1
Reject water treatment performance was investigated by whole cell anammox sludge entrapped polyvinyl alcohol/sodium alginate
gel in the stirred tank reactor (STR). The whole experiment was conducted through Phase 1 and Phase 2 in which synthetic wastewater
and modified reject water were used as feeding medium, respectively. The anammox reactor demonstrated quick start-up after
22 days as well as stable and relatively high nitrogen removal rate of more than 8.0 kg-N m−3 day−1 during the two both phases even under moderately low temperature of 25 ± 0.5°C during the last 2 months of Phase 2. The matured
brownish red PVA beads had good characteristics with buoyant density of 1.10 g cm−3, settling velocity of 141 m h−1 and diameter of 4 mm. The bacterial community was identified by 16S rDNA analysis revealing the concurrent existence of KSU-1
and new kind anammox bacterium Kumadai-I after changing influent from synthetic wastewater to reject water. It was speculated
that Kumadai-I might play a role as “promotion” factor together with KSU-1 on high nitrogen removal rate. These results demonstrate
the potential application of whole cell anammox entrapment by PVA/alginate gel for achieving stable and high-rate nitrogen
removal from high ammonium with low C/N ratio contained wastewaters, such as reject water, digester liquor or landfill leachate. 相似文献
105.
Further characterization of the binding of human recombinant interleukin 2 to heparin and identification of putative binding sites 总被引:1,自引:1,他引:1
We have previously provided compelling evidence that human recombinant
interleukin 2 (IL-2) binds to the sulfated polysaccharides heparin, highly
sulfated heparan sulfate and fucoidan. Here we show that IL-2 binding is
dependent on heparin chain length, but with fragments as small as 15-mers
retaining binding activity. The addition of exogenous heparin has no effect
on the in vitro biological activity of IL-2. In addition soluble IL-2
receptor alpha and beta polypeptides do not compete with heparin for the
binding of IL-2. IL-2 bound by heparin is still recognized by two IL-2
specific monoclonal antibodies, 3H9 and H2- 8, whose epitopes lie in the
amino terminal region. Murine IL-2 unlike its human counterpart fails to
bind to heparin. Human IL-2 analogs with single amino acid substitutions at
positions Lys43, Thr51, and Gln126 analogs no longer bind to heparin. By
contrast the Arg38Ala analog retains heparin full heparin binding activity.
These experimental findings together with molecular modeling studies
suggest two putative heparin binding sites on human IL-2, one involving
four basic residues, Lys48, Lys49, Lys54, and His55, and the other being a
discontinuous site comprising Lys43, Lys64, Arg81, and Arg83. Neither of
these two clusters is completely conserved in murine IL-2. Overall our data
suggest that the binding of human IL-2 to heparin and heparan sulfate does
not interfere with IL-2/IL-2 receptor interactions. Therefore, binding to
glycosaminoglycan may be a mechanism for retaining the cytokine in an
active form close to its site of secretion in the tissue, thus favoring a
paracrine role for IL-2.
相似文献
106.
A C Frantz A D McDevitt L C Pope J Kochan J Davison C F Clements M Elmeros G Molina-Vacas A Ruiz-Gonzalez A Balestrieri K Van Den Berge P Breyne E Do Linh San E O ?gren F Suchentrunk L Schley R Kowalczyk B I Kostka D ?irovi? N ?prem M Colyn M Ghirardi V Racheva C Braun R Oliveira J Lanszki A Stubbe M Stubbe N Stier T Burke 《Heredity》2014,113(5):443-453
Although the phylogeography of European mammals has been extensively investigated
since the 1990s, many studies were limited in terms of sampling distribution, the
number of molecular markers used and the analytical techniques employed, frequently
leading to incomplete postglacial recolonisation scenarios. The broad-scale genetic
structure of the European badger (Meles meles) is of interest as it may
result from historic restriction to glacial refugia and/or recent anthropogenic
impact. However, previous studies were based mostly on samples from western Europe,
making it difficult to draw robust conclusions about the location of refugia,
patterns of postglacial expansion and recent demography. In the present study,
continent-wide sampling and analyses with multiple markers provided evidence for two
glacial refugia (Iberia and southeast Europe) that contributed to the genetic
variation observed in badgers in Europe today. Approximate Bayesian computation
provided support for a colonisation of Scandinavia from both Iberian and southeastern
refugia. In the whole of Europe, we observed a decline in genetic diversity with
increasing latitude, suggesting that the reduced diversity in the peripheral
populations resulted from a postglacial expansion processes. Although MSVAR v.1.3
also provided evidence for recent genetic bottlenecks in some of these peripheral
populations, the simulations performed to estimate the method''s power to
correctly infer the past demography of our empirical populations suggested that the
timing and severity of bottlenecks could not be established with certainty. We urge
caution against trying to relate demographic declines inferred using MSVAR with
particular historic or climatological events. 相似文献
107.
Hoon Kim D Jeon Choi S Kook S Kim W Keun Song W 《Biochemical and biophysical research communications》2003,300(1):141-148
We previously demonstrated caspase-mediated cleavage of p130cas during apoptosis and identified two caspase-3 cleavage sites [1]. In this study, we investigated the phosphorylation-dependent cleavage of p130cas in apoptotic Rat-1 fibroblast cells. Lysophosphatidic acid and fibronectin induced p130cas phosphorylation, which in turn resulted in resistance to caspase-mediated cleavage. Alternatively, dephosphorylation by calf intestinal alkaline phosphatase, PP1, and LAR stimulated cleavage of p130cas by caspase-3, generating a 31-kDa fragment. During apoptosis, p130cas dephosphorylation seems to precede its cleavage. The phosphorylation of tyrosine and serine residues immediately adjacent to the two cleavage sites (DVPD(416) and DSPD(748)) strongly affected p130cas cleavage by caspase-3, both in vitro and in vivo. Furthermore, the generation of the 31-kDa cleavage fragment was strongly regulated by phosphorylation of a tyrosine residue at position 751 (DSPD(748) and GQY(751)). Our results collectively suggest that degradation of p130cas during apoptosis is modulated in a phosphorylation-dependent manner. 相似文献
108.
A selective molecularly imprinted polymer for immobilization of acetylcholinesterase (AChE): an active enzyme targeted and efficient method 下载免费PDF全文
Gökhan Demirci Yasemin İspirli Doğaç Mustafa Teke 《Journal of molecular recognition : JMR》2015,28(11):645-650
In the present study, we immobilized acetylcholinesterase (AChE) enzyme onto acetylcholine removed imprinted polymer and acetylcholine containing polymer. First, the polymers were produced with acetylcholine, substrate of AChE, by dispersion polymerization. Then, the enzyme was immobilized onto the polymers by using two different methods: In the first method (method A), acetylcholine was removed from the polymer, and then AChE was immobilized onto this polymer (acetylcholine removed imprinted polymer). In the second method (method B), AChE was immobilized onto acetylcholine containing polymer by affinity. In method A, enzyme‐specific species (binding sites) occurred by removing acetylcholine from the polymer. The immobilized AChE reached 240% relative specific activity comparison with free AChE because the active enzyme molecules bounded onto the polymer. Transmission electron microscopy results were taken before and after immobilization of AChE for the assessment of morphological structure of polymer. Also, the experiments, which include optimum temperature (25–65°C), optimum pH (3–10), thermal stability (4–70°C), kinetic parameters, operational stability and reusability, were performed to determine the characteristic of the immobilized AChE. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
109.
Yu‐Sin Jang Alok Malaviya Joungmin Lee Jung Ae Im Sang Yup Lee Julia Lee Moon‐Ho Eom Jung‐Hee Cho Do Young Seung 《Biotechnology progress》2013,29(4):1083-1088
Butanol is considered as a superior biofuel, which is conventionally produced by clostridial acetone‐butanol‐ethanol (ABE) fermentation. Among ABE, only butanol and ethanol can be used as fuel alternatives. Coproduction of acetone thus causes lower yield of fuel alcohols. Thus, this study aimed at developing an improved Clostridium acetobutylicum strain possessing enhanced fuel alcohol production capability. For this, we previously developed a hyper ABE producing BKM19 strain was further engineered to convert acetone into isopropanol. The BKM19 strain was transformed with the plasmid pIPA100 containing the sadh (primary/secondary alcohol dehydrogenase) and hydG (putative electron transfer protein) genes from the Clostridium beijerinckii NRRL B593 cloned under the control of the thiolase promoter. The resulting BKM19 (pIPA100) strain produced 27.9 g/l isopropanol‐butanol‐ethanol (IBE) as a fuel alcohols with negligible amount of acetone (0.4 g/l) from 97.8 g/l glucose in lab‐scale (2 l) batch fermentation. Thus, this metabolically engineered strain was able to produce 99% of total solvent produced as fuel alcohols. The scalability and stability of BKM19 (pIPA100) were evaluated at 200 l pilot‐scale fermentation, which showed that the fuel alcohol yield could be improved to 0.37 g/g as compared to 0.29 g/g obtained at lab‐scale fermentation, while attaining a similar titer. To the best of our knowledge, this is the highest titer of IBE achieved and the first report on the large scale fermentation of C. acetobutylicum for IBE production. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:1083–1088, 2013 相似文献
110.
Dong Up Song Young Do Jung Kee Oh Chay Min A Chung Kee Hyung Lee Sung Yeul Yang Boo Ahn Shin Bong Whan Ahn 《Archives of biochemistry and biophysics》2002,397(2):424-429
Tea catechins and other flavonoids have been shown to potentially protect against chronic cardiovascular diseases such as coronary heart disease and atherosclerosis. In this study, 6-month-old female Sprague-Dawley rats were fed green tea extract (50 mg/100 ml in drinking water) up to the age of 22 months, and the age-associated changes in Maillard-type fluorescence and carbonyl groups in the aortic and skin collagen were compared with those occurring in the water-fed control animals. Collagen-linked Maillard-type fluorescence was found to increase in both the aortic and skin tissues as animals aged. The age-associated increase in the fluorescence in the aortic collagen was remarkably inhibited by the green tea extract treatment, while that occurring in the skin collagen was not significantly inhibited by the treatment. The collagen carbonyl content also increased in both the aortic and skin tissues as animals aged. In contrast with the case of Maillard-type fluorescence, however, the age-associated increase in the carbonyl content was not inhibited by the green tea extract treatment either in the aortic or skin collagen. These results suggest that the inhibition of AGE formation in collagen is an important mechanism for the protective effects of tea catechins against cardiovascular diseases. 相似文献