全文获取类型
收费全文 | 4730篇 |
免费 | 434篇 |
国内免费 | 146篇 |
出版年
2023年 | 54篇 |
2022年 | 47篇 |
2021年 | 174篇 |
2020年 | 159篇 |
2019年 | 185篇 |
2018年 | 180篇 |
2017年 | 115篇 |
2016年 | 211篇 |
2015年 | 303篇 |
2014年 | 319篇 |
2013年 | 349篇 |
2012年 | 426篇 |
2011年 | 401篇 |
2010年 | 231篇 |
2009年 | 222篇 |
2008年 | 273篇 |
2007年 | 243篇 |
2006年 | 200篇 |
2005年 | 154篇 |
2004年 | 148篇 |
2003年 | 146篇 |
2002年 | 117篇 |
2001年 | 89篇 |
2000年 | 81篇 |
1999年 | 64篇 |
1998年 | 28篇 |
1997年 | 40篇 |
1996年 | 46篇 |
1995年 | 27篇 |
1994年 | 23篇 |
1993年 | 23篇 |
1992年 | 43篇 |
1991年 | 25篇 |
1990年 | 20篇 |
1989年 | 17篇 |
1988年 | 20篇 |
1987年 | 17篇 |
1986年 | 9篇 |
1985年 | 10篇 |
1984年 | 6篇 |
1983年 | 13篇 |
1982年 | 7篇 |
1981年 | 6篇 |
1978年 | 3篇 |
1977年 | 4篇 |
1976年 | 3篇 |
1975年 | 4篇 |
1974年 | 3篇 |
1973年 | 3篇 |
1965年 | 3篇 |
排序方式: 共有5310条查询结果,搜索用时 20 毫秒
1.
Fu Gao Pierre Chambon George Tellides Wei Kong Xiaoming Zhang Wei Li 《Biochemical and biophysical research communications》2014
Transforming growth factor-β (TGF-β) signaling has been prominently implicated in the pathogenesis of vascular remodeling, especially the initiation and progression of flow-induced vascular remodeling. Smooth muscle cells (SMCs) are the principal resident cells in arterial wall and are critical for arterial remodeling. However, the role of TGF-β signaling in SMC for flow-induced vascular remodeling remains unknown. Therefore, the goal of our study was to determine the effect of TGF-β pathway in SMC for vascular remodeling, by using a genetical smooth muscle-specific (SM-specific) TGF-β type II receptor (Tgfbr2) deletion mice model. Mice deficient in the expression of Tgfbr2 (MyhCre.Tgfbr2f/f) and their corresponding wild-type background mice (MyhCre.Tgfbr2WT/WT) underwent partial ligation of left common carotid artery for 1, 2, or 4 weeks. Then the carotid arteries were harvested and indicated that the disruption of Tgfbr2 in SMC provided prominent inhibition of vascular remodeling. And the thickening of carotid media, proliferation of SMC, infiltration of macrophage, and expression of matrix metalloproteinase (MMP) were all significantly attenuated in Tgfbr2 disruption mice. Our study demonstrated, for the first time, that the TGF-β signaling in SMC plays an essential role in flow-induced vascular remodeling and disruption can prevent this process. 相似文献
2.
Donghui Cao Jing Jiang Tetsuya Tsukamoto Ruming Liu Lin Ma Zhifang Jia Fei Kong Masanobu Oshima Xueyuan Cao 《PloS one》2015,10(3)
4-vinyl-2, 6-dimethoxyphenol (canolol) is an antioxidant phenolic compound extracted from crude canola oil. In current research, K19-C2mE transgenic mice, developing hyperplastic tumors spontaneously in the glandular stomach, were used to study the mechanisms involved in the anti-inflammation and anti-tumor effects of canolol. Tg mice receiving canolol diet had a reduced tumor incidence, to 41.2%, compared with Non-treatment Tg mice, 77.8% of which had gastric tumor (P=0.002). Besides that, the mean tumor diameter was decreased from 6.5mm to 4.5mm (P<0.001) after canolol administration. COX-2/PGE2 pathway is known to play pivotal role in inflammation-induced gastric tumorigenesis. The neutrophils and lymphocytes infiltration was suppressed significantly, and the mRNA levels of the proinflammatory cytokines COX-2, IL-1β and IL-12b were also downregulated in gastric mucosa. Additionally, immunohistochemical analysis showed that COX-2, EP2, Gαs and β-catenin, key factors involving in PGE2 signal transduction, were positive staining with higher H scores in Non-treatment Tg mice, while the expressions were suppressed significantly by 0.1% canolol (P<0.001). In addition, tumor-suppressor miR-7 was reactivated after canolol administration, and COX-2 was showed to be a functional target of miR-7 to suppress the tumor progression. In conclusion, canolol could inhibit the gastritis-related tumor initiation and progression, and the suppression effect was correlated with the blocking up of canonical COX-2/PGE2 signaling pathway and might be regulated by miR-7. 相似文献
3.
4.
Shiping Yang Shaomin Lin Qiang Fu Baizhen Cai Fei Kong Guang Huang Fafen Li Han Wang 《PloS one》2015,10(3)
Background
Guidelines from the U.S. National Comprehensive Cancer Network have recommended use of concurrent chemoradiotherapy (CCRT), followed by a 3-cycles combination of platinum and 5-fluorouracil chemotherapy as standard treatment for nasopharyngeal carcinoma (NPC). The benefits of CCRT for treatment of locally advanced NPC have been established. Whether platinum and 5-fluorouracil chemotherapy should be routinely added to locally advanced NPC after CCRT is still open to debate. Whether adjuvant chemotherapy provides an additional survival benefit for the subgroup of patients with residual nasopharyngeal carcinoma who have undergone CCRT is also unclear. This retrospective study was initiated to determine the survival benefit of adjuvant chemotherapy (AC) in residual NPC patients who have undergone concurrent chemoradiotherapy.Methods
The retrospective study included 155 nasopharyngeal carcinoma patients who had local residual lesions after the platinum-based CCRT without or with AC. Kaplan-Meier analysis and the log-rank test were used to estimate overall survival (OS), failure-free survival (FFS), local relapse-free survival (LRFS) and distant metastasis-free survival (DMFS).Results
Median follow-up was 47 months. Adjuvant cisplatin or nedaplatin plus 5-fluorouracil chemotherapy did not significantly improve 3-year OS, LRFS, FFS, and DMFS for patients with residual nasopharyngeal carcinoma after undergoing CCRT. The 3-year OS rates for the no-AC group and AC group were 71.6% and 73.7%, respectively (P= 0.44). The 3-year FFS rates for no-AC group and AC group were 57.5% and 66.9%, respectively ((P= 0.19). The 3-year LRFS rates for no-AC group and AC group were 84.7% and 87.9%, respectively ((P= 0.51). The 3-year DMFS rates for no-AC group and AC group were 71.4% and 77.4%, respectively ((P= 0.23).Conclusions
Since we did not find sufficient data to support significant survival in 3-year OS, LRFS, FFS, and DMFS, whether Adjuvant cisplatin or nedaplatin and 5-fluorouracil chemotherapy should be routinely added to residual nasopharyngeal carcinoma patients after undergoing CCRT remain uncertain. 相似文献5.
The interfacial electron transfer of glucose oxidase (GOx) on a poly(glutamic acid)-modified glassy carbon electrode (PGA/GCE) was investigated. The redox peaks measured for GOx and flavin adenine dinucleotide (FAD) are similar, and the anodic peak of GOx does not increase in the presence of glucose in a mediator-free solution. These indicate that the electroactivity of GOx is not the direct electron transfer (DET) between GOx and PGA/GCE and that the observed electroactivity of GOx is ascribed to free FAD that is released from GOx. However, efficient electron transfer occurred if an appropriate mediator was placed in solution, suggesting that GOx is active. The PGA/GCE-based biosensor showed wide linear response in the range of 0.5–5.5 mM with a low detection limit of 0.12 mM and high sensitivity and selectivity for measuring glucose. 相似文献
6.
Transition from Diffusion‐Controlled Intercalation into Extrinsically Pseudocapacitive Charge Storage of MoS2 by Nanoscale Heterostructuring 下载免费PDF全文
Qasim Mahmood Sul Ki Park Kideok D. Kwon Sung‐Jin Chang Jin‐Yong Hong Guozhen Shen Young Mee Jung Tae Jung Park Sung Woon Khang Woo Sik Kim Jing Kong Ho Seok Park 《Liver Transplantation》2016,6(1)
2D nanomaterials have been found to show surface‐dominant phenomena and understanding this behavior is crucial for establishing a relationship between a material's structure and its properties. Here, the transition of molybdenum disulfide (MoS2) from a diffusion‐controlled intercalation to an emergent surface redox capacitive behavior is demonstrated. The ultrafast pseudocapacitive behavior of MoS2 becomes more prominent when the layered MoS2 is downscaled into nanometric sheets and hybridized with reduced graphene oxide (RGO). This extrinsic behavior of the 2D hybrid is promoted by the fast Faradaic charge‐transfer kinetics at the interface. The heterostructure of the 2D hybrid, as observed via high‐angle annular dark field–scanning transmission electron microscopy and Raman mapping, with a 1T MoS2 phase at the interface and a 2H phase in the bulk is associated with the synergizing capacitive performance. This 1T phase is stabilized by the interactions with the RGO. These results provide fundamental insights into the surface effects of 2D hetero‐nanosheets on emergent electrochemical properties. 相似文献
7.
Antrodia camphorata is a well-known medicinal mushroom in Taiwan and has been studied for decades, especially with focus on anti-cancer activity. Polysaccharides are the major bioactive compounds reported with anti-cancer activity, but the debates on how they target cells still remain. Research addressing the encapsulation of polysaccharides from A. camphorata extract (ACE) to enhance anti-cancer activity is rare. In this study, ACE polysaccharides were nano-encapsulated in chitosan-silica and silica (expressed as ACE/CS and ACE/S, respectively) to evaluate the apoptosis effect on a hepatoma cell line (Hep G2). The results showed that ACE polysaccharides, ACE/CS and ACE/S all could damage the Hep G2 cell membrane and cause cell death, especially in the ACE/CS group. In apoptosis assays, DNA fragmentation and sub-G1 phase populations were increased, and the mitochondrial membrane potential decreased significantly after treatments. ACE/CS and ACE/S could also increase reactive oxygen species (ROS) generation, induce Fas/APO-1 (apoptosis antigen 1) expression and elevate the proteolytic activities of caspase-3, caspase-8 and caspase-9 in Hep G2 cells. Unsurprisingly, ACE/CS induced a similar apoptosis mechanism at a lower dosage (ACE polysaccharides = 13.2 μg/mL) than those of ACE/S (ACE polysaccharides = 21.2 μg/mL) and ACE polysaccharides (25 μg/mL). Therefore, the encapsulation of ACE polysaccharides by chitosan-silica nanoparticles may provide a viable approach for enhancing anti-tumor efficacy in liver cancer cells. 相似文献
8.
9.
Li Yu Dachuan Shi Junling Li Yingzhen Kong Yanchong Yu Guohua Chai Ruibo Hu Juan Wang Michael G. Hahn Gongke Zhou 《Plant physiology》2014,164(4):1842-1856
Mannans are hemicellulosic polysaccharides that are considered to have both
structural and storage functions in the plant cell wall. However, it is not yet known
how mannans function in Arabidopsis (Arabidopsis thaliana) seed
mucilage. In this study, CELLULOSE SYNTHASE-LIKE A2
(CSLA2; At5g22740) expression was observed in several seed
tissues, including the epidermal cells of developing seed coats. Disruption of
CSLA2 resulted in thinner adherent mucilage halos, although the
total amount of the adherent mucilage did not change compared with the wild type.
This suggested that the adherent mucilage in the mutant was more compact compared
with that of the wild type. In accordance with the role of CSLA2 in glucomannan
synthesis, csla2-1 mucilage contained 30% less mannosyl and glucosyl
content than did the wild type. No appreciable changes in the composition, structure,
or macromolecular properties were observed for nonmannan polysaccharides in mutant
mucilage. Biochemical analysis revealed that cellulose crystallinity was
substantially reduced in csla2-1 mucilage; this was supported by the
removal of most mucilage cellulose through treatment of csla2-1
seeds with endo-β-glucanase. Mutation in CSLA2 also resulted
in altered spatial distribution of cellulose and an absence of birefringent cellulose
microfibrils within the adherent mucilage. As with the observed changes in
crystalline cellulose, the spatial distribution of pectin was also modified in
csla2-1 mucilage. Taken together, our results demonstrate that
glucomannans synthesized by CSLA2 are involved in modulating the structure of
adherent mucilage, potentially through altering cellulose organization and
crystallization.Mannan polysaccharides are a complex set of hemicellulosic cell wall polymers that are
considered to have both structural and storage functions. Based on the particular chemical
composition of the backbone and the side chains, mannan polysaccharides are classified into
four types: pure mannan, glucomannan, galactomannan, and galactoglucomannan (Moreira and Filho, 2008; Wang et al., 2012; Pauly et al.,
2013). Each of these polysaccharides is composed of a β-1,4-linked
backbone containing Man or a combination of Glc and Man residues. In addition, the mannan
backbone can be substituted with side chains of α-1,6-linked Gal residues. Mannan
polysaccharides have been proposed to cross link with cellulose and other hemicelluloses
via hydrogen bonds (Fry, 1986; Iiyama et al., 1994; Obel et al., 2007; Scheller and
Ulvskov, 2010). Furthermore, it has been reported that heteromannans with
different levels of substitution can interact with cellulose in diverse ways (Whitney et al., 1998). Together, these observations
indicate the complexity of mannan polysaccharides in the context of cell wall
architecture.CELLULOSE SYNTHASE-LIKE A (CSLA) enzymes have been shown to have mannan synthase activity
in vitro. These enzymes polymerize the β-1,4-linked backbone of mannans or
glucomannans, depending on the substrates (GDP-Man and/or GDP-Glc) provided (Richmond and Somerville, 2000; Liepman et al., 2005, 2007;
Pauly et al., 2013). In Arabidopsis
(Arabidopsis thaliana), nine CSLA genes have been
identified; different CSLAs are responsible for the synthesis of different
mannan types (Liepman et al., 2005, 2007). CSLA7 has mannan synthase activity in vitro
(Liepman et al., 2005) and has been shown to
synthesize stem glucomannan in vivo (Goubet et al.,
2009). Disrupting the CSLA7 gene results in defective pollen
growth and embryo lethality phenotypes in Arabidopsis, indicating structural or signaling
functions of mannan polysaccharides during plant embryo development (Goubet et al., 2003). A mutation in CSLA9 results in
the inhibition of Agrobacterium tumefaciens-mediated root transformation
in the rat4 mutant (Zhu et al.,
2003). CSLA2, CSLA3, and CSLA9 are proposed to play nonredundant roles in the
biosynthesis of stem glucomannans, although mutations in CSLA2,
CSLA3, or CSLA9 have no effect on stem development or
strength (Goubet et al., 2009). All of the
Arabidopsis CSLA proteins have been shown to be involved in the biosynthesis of mannan
polysaccharides in the plant cell wall (Liepman et al.,
2005, 2007), although the precise
physiological functions of only CSLA7 and CSLA9 have been conclusively demonstrated.In Arabidopsis, when mature dry seeds are hydrated, gel-like mucilage is extruded to
envelop the entire seed. Ruthenium red staining of Arabidopsis seeds reveals two different
mucilage layers, termed the nonadherent and the adherent mucilage layers (Western et al., 2000; Macquet et al., 2007a). The outer, nonadherent mucilage is loosely
attached and can be easily extracted by shaking seeds in water. Compositional and linkage
analyses suggest that this layer is almost exclusively composed of unbranched
rhamnogalacturonan I (RG-I) (>80% to 90%), with
small amounts of branched RG-I, arabinoxylan, and
high methylesterified homogalacturonan (HG). By
contrast, the inner, adherent mucilage layer is tightly attached to the seed and can only
be removed by strong acid or base treatment, or by enzymatic digestion (Macquet et al., 2007a; Huang et al., 2011; Walker et al.,
2011). As with the nonadherent layer, adherent mucilage is also mainly composed
of unbranched RG-I, but with small numbers of
arabinan and galactan ramifications (Penfield et al.,
2001; Willats et al., 2001; Dean et al., 2007; Macquet et al., 2007a, 2007b; Arsovski et al., 2009; Haughn and Western, 2012). There are also minor amounts of pectic
HG in the adherent mucilage, with high
methylesterified HG in the external domain compared
with the internal domain of the adherent layer (Willats
et al., 2001; Macquet et al., 2007a;
Rautengarten et al., 2008; Sullivan et al., 2011; Saez-Aguayo et al., 2013). In addition, the adherent mucilage
contains cellulose (Blake et al., 2006; Macquet et al., 2007a), which is entangled with RG-I and is thought to anchor the pectin-rich mucilage
onto seeds (Macquet et al., 2007a; Harpaz-Saad et al., 2011, 2012; Mendu et al., 2011;
Sullivan et al., 2011). As such, Arabidopsis
seed mucilage is considered to be a useful model for investigating the biosynthesis of cell
wall polysaccharides and how this process is regulated in vivo (Haughn and Western, 2012).Screening for altered seed coat mucilage has led to the identification of several genes
encoding enzymes that are involved in the biosynthesis or modification of mucilage
components. RHAMNOSE SYNTHASE2/MUCILAGE-MODIFIED4 (MUM4) is responsible for the synthesis
of UDP-l-Rha (Usadel et al., 2004; Western et al., 2004; Oka et al., 2007). The putative GALACTURONSYLTRANSFERASE11 can
potentially synthesize mucilage RG-I or HG pectin from UDP-d-GalUA (Caffall et al., 2009). GALACTURONSYLTRANSFERASE-LIKE5
appears to function in the regulation of the final size of the mucilage RG-I (Kong et al.,
2011, 2013). Mutant seeds defective in
these genes display reduced thickness of the extruded mucilage layer compared with
wild-type Arabidopsis seeds.RG-I deposited in the apoplast of seed coat
epidermal cells appears to be synthesized in a branched form that is subsequently modified
by enzymes in the apoplast. MUM2 encodes a β-galactosidase that
removes Gal residues from RG-I side chains (Dean et al., 2007; Macquet et al., 2007b). β-XYLOSIDASE1 encodes an
α-l-arabinfuranosidase that removes Ara residues from RG-I side chains (Arsovski et al., 2009). Disruptions of these genes lead to defective hydration
properties and affect the extrusion of mucilage. Furthermore, correct methylesterification
of mucilage HG is also required for mucilage
extrusion. HG is secreted into the wall in a high
methylesterified form that can then be enzymatically demethylesterified by pectin
methylesterases (PMEs; Bosch and Hepler, 2005). PECTIN METHYLESTERASE INHIBITOR6 (PMEI6)
inhibits PME activities (Saez-Aguayo et al., 2013). The subtilisin-like Ser protease (SBT1.7)
can activate other PME inhibitors, but not PMEI6
(Rautengarten et al., 2008; Saez-Aguayo et al., 2013). Disruption of either
PMEI6 or SBT1.7 results in the delay of mucilage
release.Although cellulose is present at low levels in adherent mucilage, it plays an important
adhesive role for the attachment of mucilage pectin to the seed coat epidermal cells. The
orientation and amount of pectin associated with the cellulose network is largely
determined by cellulose conformation properties (Macquet
et al., 2007a; Haughn and Western,
2012). Previous studies have demonstrated that CELLULOSE SYNTHASE A5 (CESA5) is
required for the production of seed mucilage cellulose and the adherent mucilage in the
cesa5 mutant can be easily extracted with water (Harpaz-Saad et al., 2011, 2012; Mendu et al., 2011; Sullivan et al., 2011).Despite all of these discoveries, large gaps remain in the current knowledge of the
biosynthesis and functions of mucilage polysaccharides in seed coats. In this study, we
show that CSLA2 is involved in the biosynthesis of mucilage glucomannan. Furthermore, we
show that CSLA2 functions in the maintenance of the normal structure of the adherent
mucilage layer through modifying the mucilage cellulose ultrastructure. 相似文献
10.
Huayan Yin Xuye Du Biao Wang Xin Ma Cunyao Bo Anfei Li Xiaocun Zhang Lingrang Kong 《Molecular breeding : new strategies in plant improvement》2017,37(8):97
High-molecular-weight glutenin subunits (HMW-GS) in wheat grain are the major determinants of dough elasticity and viscosity and thus of bread-making quality. PCR-based molecular markers designed based on DNA polymorphisms were used to analyze HMW-GS genes in wheat. The loop-mediated isothermal amplification (LAMP) assay is a simple and rapid method for specific detection of genomic DNA target sequences. In the present study, we designed a set of LAMP markers by targeting the unique sequences of 1Dx2 and 1Dx5 genes. The primers could effectively distinguish the 1Dx2 and 1Dx5 genes from other genes at the Glu-1 locus. The results were confirmed by agarose gel electrophoresis. For visualization, ethidium bromide was used, and fluorescence only appeared in the positive samples. Under optimal conditions, the detection could be finished in 1 h. Thirty-eight wheat cultivars with known HMW-GS were used to validate LAMP markers for 1Dx2 and 1Dx5 genes. Only DNA samples with target genes could be amplified, and the results could be read easily using this method. The tests using LAMP were easy to perform, rapid, and sensitive. Thus, the current study results have the potential to be a powerful tool for the detection of HMW-GS genes in wheat. 相似文献