全文获取类型
收费全文 | 4593篇 |
免费 | 384篇 |
国内免费 | 2篇 |
专业分类
4979篇 |
出版年
2023年 | 24篇 |
2022年 | 61篇 |
2021年 | 119篇 |
2020年 | 62篇 |
2019年 | 83篇 |
2018年 | 123篇 |
2017年 | 94篇 |
2016年 | 172篇 |
2015年 | 221篇 |
2014年 | 273篇 |
2013年 | 338篇 |
2012年 | 433篇 |
2011年 | 353篇 |
2010年 | 236篇 |
2009年 | 196篇 |
2008年 | 261篇 |
2007年 | 234篇 |
2006年 | 220篇 |
2005年 | 203篇 |
2004年 | 196篇 |
2003年 | 166篇 |
2002年 | 155篇 |
2001年 | 36篇 |
2000年 | 43篇 |
1999年 | 50篇 |
1998年 | 54篇 |
1997年 | 25篇 |
1996年 | 24篇 |
1995年 | 25篇 |
1994年 | 25篇 |
1993年 | 21篇 |
1992年 | 26篇 |
1991年 | 20篇 |
1990年 | 30篇 |
1989年 | 21篇 |
1988年 | 20篇 |
1987年 | 22篇 |
1986年 | 12篇 |
1985年 | 20篇 |
1984年 | 26篇 |
1983年 | 18篇 |
1982年 | 17篇 |
1981年 | 18篇 |
1980年 | 19篇 |
1979年 | 17篇 |
1978年 | 17篇 |
1977年 | 8篇 |
1974年 | 10篇 |
1964年 | 7篇 |
1962年 | 7篇 |
排序方式: 共有4979条查询结果,搜索用时 15 毫秒
121.
Ana Casa?al Ulrich Zander Cristina Mu?oz Florine Dupeux Irene Luque Miguel Angel Botella Wilfried Schwab Victoriano Valpuesta José A. Marquez 《The Journal of biological chemistry》2013,288(49):35322-35332
Pathogenesis-related 10 (PR-10) proteins are involved in many aspects of plant biology but their molecular function is still unclear. They are related by sequence and structural homology to mammalian lipid transport and plant abscisic acid receptor proteins and are predicted to have cavities for ligand binding. Recently, three new members of the PR-10 family, the Fra a proteins, have been identified in strawberry, where they are required for the activity of the flavonoid biosynthesis pathway, which is essential for the development of color and flavor in fruits. Here, we show that Fra a proteins bind natural flavonoids with different selectivity and affinities in the low μm range. The structural analysis of Fra a 1 E and a Fra a 3-catechin complex indicates that loops L3, L5, and L7 surrounding the ligand-binding cavity show significant flexibility in the apo forms but close over the ligand in the Fra a 3-catechin complex. Our findings provide mechanistic insight on the function of Fra a proteins and suggest that PR-10 proteins, which are widespread in plants, may play a role in the control of secondary metabolic pathways by binding to metabolic intermediates. 相似文献
122.
Background
Accurate QTL mapping is a prerequisite in the search for causative mutations. Bayesian genomic selection models that analyse many markers simultaneously should provide more accurate QTL detection results than single-marker models. Our objectives were to (a) evaluate by simulation the influence of heritability, number of QTL and number of records on the accuracy of QTL mapping with Bayes Cπ and Bayes C; (b) estimate the QTL status (homozygous vs. heterozygous) of the individuals analysed. This study focussed on the ten largest detected QTL, assuming they are candidates for further characterization.Methods
Our simulations were based on a true dairy cattle population genotyped for 38 277 phased markers. Some of these markers were considered biallelic QTL and used to generate corresponding phenotypes. Different numbers of records (4387 and 1500), heritability values (0.1, 0.4 and 0.7) and numbers of QTL (10, 100 and 1000) were studied. QTL detection was based on the posterior inclusion probability for individual markers, or on the sum of the posterior inclusion probabilities for consecutive markers, estimated using Bayes C or Bayes Cπ. The QTL status of the individuals was derived from the contrast between the sums of the SNP allelic effects of their chromosomal segments.Results
The proportion of markers with null effect (π) frequently did not reach convergence, leading to poor results for Bayes Cπ in QTL detection. Fixing π led to better results. Detection of the largest QTL was most accurate for medium to high heritability, for low to moderate numbers of QTL, and with a large number of records. The QTL status was accurately inferred when the distribution of the contrast between chromosomal segment effects was bimodal.Conclusions
QTL detection is feasible with Bayes C. For QTL detection, it is recommended to use a large dataset and to focus on highly heritable traits and on the largest QTL. QTL statuses were inferred based on the distribution of the contrast between chromosomal segment effects. 相似文献123.
Maya D. Lambreva Maria Teresa Giardi Irene Rambaldi Amina Antonacci Sandro Pastorelli Ivo Bertalan Ivan Husu Udo Johanningmeier Giuseppina Rea 《PloS one》2013,8(4)
This study was prompted by increasing concerns about ecological damage and human health threats derived by persistent contamination of water and soil with herbicides, and emerging of bio-sensing technology as powerful, fast and efficient tool for the identification of such hazards. This work is aimed at overcoming principal limitations negatively affecting the whole-cell-based biosensors performance due to inadequate stability and sensitivity of the bio-recognition element. The novel bio-sensing elements for the detection of herbicides were generated exploiting the power of molecular engineering in order to improve the performance of photosynthetic complexes. The new phenotypes were produced by an in vitro directed evolution strategy targeted at the photosystem II (PSII) D1 protein of Chlamydomonas reinhardtii, using exposures to radical-generating ionizing radiation as selection pressure. These tools proved successful to identify D1 mutations conferring enhanced stability, tolerance to free-radical-associated stress and competence for herbicide perception. Long-term stability tests of PSII performance revealed the mutants capability to deal with oxidative stress-related conditions. Furthermore, dose-response experiments indicated the strains having increased sensitivity or resistance to triazine and urea type herbicides with I50 values ranging from 6×10−8 M to 2×10−6 M. Besides stressing the relevance of several amino acids for PSII photochemistry and herbicide sensing, the possibility to improve the specificity of whole-cell-based biosensors, via coupling herbicide-sensitive with herbicide-resistant strains, was verified. 相似文献
124.
Eva Villamón Ana P. Berbegall Marta Piqueras Irene Tadeo Victoria Castel Anna Djos Tommy Martinsson Samuel Navarro Rosa Noguera 《PloS one》2013,8(1)
Background/Aim
Genetic analysis in neuroblastoma has identified the profound influence of MYCN amplification and 11q deletion in patients’ prognosis. These two features of high-risk neuroblastoma usually occur as mutually exclusive genetic markers, although in rare cases both are present in the same tumor. The purpose of this study was to characterize the genetic profile of these uncommon neuroblastomas harboring both these high-risk features.Methods
We selected 18 neuroblastomas with MNA plus 11q loss detected by FISH. Chromosomal aberrations were analyzed using Multiplex Ligation-dependent Probe Amplification and Single Nucleotide Polymorphism array techniques.Results and Conclusion
This group of tumors has approximately the same high frequency of aberrations as found earlier for 11q deleted tumors. In some cases, DNA instability generates genetic heterogeneity, and must be taken into account in routine genetic diagnosis. 相似文献125.
We have used the HLA-C-specific DNA probe pC250 to investigate restriction fragment length polymorphism (RFLP) at the HLA-C locus. Genomic Southern blot hybridization included DNA prepared from a panel of homozygous typing cells representing serological specificities Cw1 to Cw8 and also from samples representing Cw blanks. Although many restriction nucleases failed to reveal any polymorphism, RFLPs were evident with Taq I, Pvu II, Bst XI, Nde 1, and Nci I in addition to the previously reported Eco RI. In the case of Bst XI, a unique RFLP defined a subset of serologically defined Cw blanks. Comparison of RFLP sizes with restriction fragment lengths obtained from the known HLA-Cw3 gene sequence permitted the localization of intragenic C locus RFLLs and the identification of a variable Taq I site in the second intron, a variable Nci I site near the end of the fourth exon, and a variable Pvu lI site in the fifth intron. 相似文献
126.
Interstitial cells of Cajal: mediators of communication between circular and longitudinal muscle layers of canine colon 总被引:3,自引:0,他引:3
Louis W. C. Liu Laura Farraway Irene Berezin J. D. Huizinga 《Cell and tissue research》1998,294(1):69-79
The network of interstitial cells of Cajal associated with Auerbach’s (myenteric) plexus in the canine colon was investigated
to determine its role in facilitating communication between circular and longitudinal muscle layers. Electrical coupling between
the muscle layers was demonstrated by propagating extracellularly evoked electrotonic pulses from circular muscle cells to
nearby longitudinal muscle cells. The likelihood of cytoplasmic continuity across Auerbach’s plexus was further demonstrated
by the ability of neurobiotin to spread between the interstitial cells and the circular and longitudinal muscle cells. Importantly,
direct neurobiotin spread between circular and longitudinal muscle cells was not observed even when they were in close proximity
as determined by confocal microscopy. When neurobiotin did spread across the two muscle layers, the intervening interstitial
cells were always neurobiotin-positive. In regions where circular and longitudinal muscle cells approach each other closely,
electron microscopy revealed the presence of close appositions between interstitial cells and smooth muscle cells. Gap junctions
between interstitial cells and smooth muscle cells of both layers, as judged by electron microscopy, were extremely rare.
Neither gap junctions nor close appositions were observed between longitudinal and circular muscle cells. The special arrangement
for electrotonic coupling across Auerbach’s plexus through interstitial cells of Cajal suggests controlled coupling between
the two muscle layers, explaining the preservation of their distinct electrical activities.
Received: 21 July 1995 / Accepted: 22 April 1998 相似文献
127.
Several pentahalophenylplatinate complexes with Pt-Sn metal-metal bonds have been synthesized by facile insertion of SnCl2 into Pt-Cl bonds of the starting platinum substrates. The complexes have been characterized spectroscopically and, in the case of (NBu4)2[trans-Pt(SnCl3)2(C6F5)2] and (NBu4)2[trans-Pt2(μ-Cl)2(SnCl3)2(C6F5)2], the structures have been analyzed by X-ray diffraction. The reactivity of these derivatives towards neutral ligands has been explored. The electronic spectra of some selected derivatives have also been examined. 相似文献
128.
Tai On Yau Thomas Ho Yin Leung Sandra Lam Oi Fung Cheung Edmund Kwok Kwan Tung Pek Lan Khong Amy Lam Sookja Chung Irene Oi Lin Ng 《PloS one》2009,4(8)
DLC2 (deleted in liver cancer 2), a Rho GTPase-activating protein, was previously shown to be underexpressed in human hepatocellular carcinoma and has tumor suppressor functions in cell culture models. We generated DLC2-deficient mice to investigate the tumor suppressor role of DLC2 in hepatocarcinogenesis and the function of DLC2 in vivo. In this study, we found that, unlike homologous DLC1, which is essential for embryonic development, DLC2 was dispensable for embryonic development and DLC2-deficient mice could survive to adulthood. We also did not observe a higher incidence of liver tumor formation or diethylnitrosamine (DEN)-induced hepatocarcinogenesis in DLC2-deficient mice. However, we observed that DLC2-deficient mice were smaller and had less adipose tissue than the wild type mice. These phenotypes were not due to reduction of cell size or defect in adipogenesis, as observed in the 190B RhoGAP-deficient mouse model. Together, these results suggest that deficiency in DLC2 alone does not enhance hepatocarcinogenesis. 相似文献
129.
Øyvind M. Andersen Monica Jordheim Angella Mbabazi Irene Skaar 《Phytochemistry》2010,71(13):1558-1563
Four anthocyanins, cyanidin 3-O-(2″-(5?-(E-p-coumaroyl)-β-apiofuranosyl)-β-xylopyranoside)-5-O-β-glucopyranoside, cyanidin 3-O-(2″-(5?-(E-p-coumaroyl)-β-apiofuranosyl)-β-xylopyranoside), cyanidin 3-O-(2″-(5?-(E-caffeoyl)-β-apiofuranosyl)-β-xylopyranoside) and cyanidin 3-O-(2″-(5?-(E-feroyl)-β-apiofuranosyl)-β-xylopyranoside) were isolated from leaves of African milk bush, (Synadeniumgrantii Hook, Euphorbiaceae) together with the known cyanidin 3-O-β-xylopyranoside-5-O-β-glucopyranoside and cyanidin 3-O-β-xyloside. The four former pigments are the first reported anthocyanins containing the monosaccharide apiose, and the three 5?-cinnamoyl derivative-2″-(β-apiosyl)-β-xyloside subunits have previously not been reported for any compound. 相似文献
130.
Taxol is an anticancer drug that triggers apoptosis in a wide spectrum of cancers such as ovarian, breast, lung, head and neck, and bladder carcinoma by both caspase-dependent and -independent apoptosis mechanisms. However, the exact signaling pathways involved in taxol-induced apoptosis strongly depend on the cellular background and they are not completely established yet. In this study we demonstrate that taxol induces caspase-3-independent apoptosis in NIH3T3 cells by a calpain-mediated mechanism. Taxol treatment produced changes in the mitochondrial membrane potential (Delta Psi m) which could be responsible of Ca(2+) release from the mitochondria and the consequent calpain activation. Interestingly, we show that calpain produced proteolysis of caspase-3 and demonstrate that, accordingly, calpain inhibition increased taxol-induced apoptosis. In addition, we reveal that poly (ADP-ribose) polymerase (PARP) was processed by calpain in taxol-treated cells and by caspase-3 after calpain inhibition. In conclusion, these results demonstrate for the first time that calpain could play an important role modulating taxol-induced apoptosis. Further studies are needed to address the potentiality of inducing apoptosis by a combined use of taxol and calpain inhibitors in cells with increased calpain activity. 相似文献