全文获取类型
收费全文 | 7654篇 |
免费 | 451篇 |
国内免费 | 22篇 |
出版年
2023年 | 94篇 |
2022年 | 141篇 |
2021年 | 373篇 |
2020年 | 357篇 |
2019年 | 502篇 |
2018年 | 404篇 |
2017年 | 285篇 |
2016年 | 383篇 |
2015年 | 415篇 |
2014年 | 508篇 |
2013年 | 670篇 |
2012年 | 622篇 |
2011年 | 623篇 |
2010年 | 322篇 |
2009年 | 280篇 |
2008年 | 334篇 |
2007年 | 323篇 |
2006年 | 279篇 |
2005年 | 242篇 |
2004年 | 185篇 |
2003年 | 131篇 |
2002年 | 114篇 |
2001年 | 44篇 |
2000年 | 29篇 |
1999年 | 43篇 |
1998年 | 26篇 |
1997年 | 24篇 |
1996年 | 20篇 |
1995年 | 16篇 |
1994年 | 11篇 |
1993年 | 28篇 |
1992年 | 14篇 |
1991年 | 38篇 |
1990年 | 21篇 |
1989年 | 24篇 |
1988年 | 12篇 |
1987年 | 22篇 |
1986年 | 16篇 |
1985年 | 18篇 |
1984年 | 16篇 |
1983年 | 10篇 |
1982年 | 13篇 |
1981年 | 13篇 |
1980年 | 12篇 |
1979年 | 6篇 |
1978年 | 7篇 |
1976年 | 7篇 |
1974年 | 8篇 |
1973年 | 7篇 |
1972年 | 7篇 |
排序方式: 共有8127条查询结果,搜索用时 796 毫秒
991.
Santosh Kumar Ramachandra Jadhav Krunal Arvind Patel Bhushan Bhalchandra Dholakia Bashir Mohammad Khan 《Bioinformation》2012,8(19):943-949
Medicinal plants are extensively utilized in traditional and herbal medicines, both in India and around the world due to the
presence of diverse low molecular weight natural products such as flavonoids, alkaloids, terpenoids and sterols. Flavonoids which
have health benefits for humans are the large class of phenylpropanoid-derived secondary metabolites and are mostly glycosylated
by UDP-glycosyltransferases (UGTs). Although large numbers of different UGTs are known from higher plants, very few protein
structures have been reported till now. In the present study, the three-dimensional model of flavonoid specific glycosyltransferases
(WsFGT) from Withania somnifera was constructed based on the crystal structure of plant UGTs. The resulted model was assessed
by various tools and the final refined model revealed GT-B type fold. Further, to understand the sugar donors and acceptors
interactions with the active site of WsFGT, docking studies were performed. The amino acids from conserved PSPG box were
interacted with sugar donor while His18, Asp110, Trp352 and Asn353 were important for catalytic function. This structural and
docking information will be useful to understand the glycosylation mechanism of flavonoid glucosides.
Abbreviations
DOPE - Discrete Optimized Potential Energy, PDB - Protein Data Bank, PSPG - Plant Secondary Product Glycosyltransferase, RMSD - Root Mean Squared Deviation, UDP - Uridine diphosphate, UGT - UDP-glycosyltransferases. 相似文献992.
993.
Poliovirus causes flaccid paralysis through the destruction of motor neurons in the CNS. Susceptibility to its infection is mainly due
to the interaction in between the surface capsid proteins and its receptors on the host cell surface, important for binding,
penetration and other necessary events during early infection. Receptor modification is a new approach to treat viral diseases by
the modification of target proteins structure. Binding domains are modified in an effective way to make it difficult for the virus to
recognize it. In this study, tolerant and intolerant induced mutations in the poliovirus receptor, VP1 and VP2 were identified and
substituted in the seed sequence to get the modified versions. Substitutions causing changes in initial folding were short listed and
further analyzed for high level folding, physiochemical properties and interactions. Highest RMSD values were observed in
between the seed and the mutant K90F (3.265 Å) and Q130W (3.270Å) respectively. The proposed substitutions were found to have
low functional impact and thus can be further tested and validated by the experimental researchers. Interactions analyses proved
most of the substitutions having decreased affinity for both the VP1 and VP2 and thus are of significant importance against
poliovirus. This study will play an important role for bridging computational biology to other fields of applied biology and also
will provide an insight to develop resistance against viral diseases. It is also expected that same approach can also be applicable
against other viruses like HCV, HIV and other in near future. 相似文献
994.
995.
996.
Voice impairments, attention to increased unhealthy social behavior and voice abuse, have been increasing dramatically. Therefore, diagnosis of voice diseases has an important role in the opportune treatment of pathologic voices. This paper presents an extensive study in identification of different voice disorders which their origin is in the vocal folds. Firstly, a qualitative study is applied based on short-time Fourier transform (STFT) and continuous wavelet transform (CWT) in order to investigate their aptitude in the presentation of discriminative features to identify disordered voices from normal ones. Therefore, wavelet packet transform (WPT) for their ability to analyze scrutinizingly a signal at several levels of resolution is chosen as strong speech signal parameterization method. The ability of energy and entropy features, obtained from the coefficients in the output nodes of the optimum wavelet packet tree, is investigated. Linear discriminant analysis (LDA) and principal component analysis (PCA) are evaluated as feature dimension reduction methods in order to optimize recognition algorithm. The performance of each structure is evaluated in terms of the accuracy, sensitivity, specificity, and area under the receiver operating curve (AUC). Eventually, entropy features in the sixth level of WPT decomposition along with feature dimension reduction by LDA and a support vector machine-based classification method is the most optimum algorithm that leads to the recognition rate of 100% and AUC of 100%. Proposed system clearly outperforms previous works in both respect of accuracy and reduction of residues; which may lead in full accuracy and high speed diagnosis procedure. 相似文献
997.
Guanine nucleotide exchange factors (GEFs) regulate the activity of small G proteins by catalysing the intrinsically slow exchange of GDP for GTP. The mechanism involves the formation of trimeric G protein-nucleotide-GEF complexes, followed by the release of nucleotide to form stable binary G protein-GEF complexes. A number of structural studies of G protein-GEF complexes have shown large structural changes induced in the nucleotide binding site. Together with a recent structure of a trimeric complex, these studies have suggested not only some common principles but also large differences in detail in the GEF-mediated exchange reaction. Several structures suggested that a glutamic acid residue in switch II, which is part of the DxxGQE motif and highly conserved in Ras-like G proteins, might have a decisive mechanistic role in GEF-mediated nucleotide exchange reactions. Here we show that mutation of the switch II glutamate to Ala severely impairs GEF-catalysed nucleotide exchange in most, but not all, Ras family G proteins, explaining its high sequence conservation. The residue determines the initial approach of GEF to the nucleotide-loaded G protein and does not appreciably affect the formation of a binary nucleotide-free complex. Its major effect thus appears to be the removal of the P-loop lysine from its interaction with the nucleotide. 相似文献
998.
Ahmad Ali Muhammad Abdullah Masroor Ellahi Babar Khalid Javed Asif Nadeem 《Journal of genetics》2008,87(3):219-227
An investigation to understand the dynamics and biological significance of fragile site expression, and identification of
5-fluorodeoxyuridine (FUdR) induced chromosomal gaps/breaks, were carried out in an experimental flock of 45 Suffolk sheep.
The statistical comparison revealed, highly significant variation in the frequency of chromosomal fragile site expression
between control and FUdR cultures. Mean (± S.D.) values for cells with gaps and breaks, or aberrant cell count (AC), and the
number of aberrations (NoA) per animal were 2.02 ± 0.34, 2.42 ± 0.48, 13.26 ± 0.85 and 21.87 ± 1.88 (P < 0.01) in control and FUdR cultures, respectively. The comparison of age revealed nonsignificant variation between control
and FUdR cultures. The G-band analysis of fragile site data revealed gaps in 29 autosomal and two X-chromosomal bands in the
control cultures, whereas FUdR treated cultures scored 78 unstable bands in autosomes of which 56 were significantly fragile.
X-chromosomes expressed breaks and gaps in six G-negative bands and five of them (Xq13, Xq15, Xq17, Xq24 and Xq26) were significantly
fragile. The distribution comparison of autosomal fragile sites between sex groups did not reveal any significant variation.
Female X-chromosomes were significantly more fragile than the male X-chromosomes. The distribution comparison for age groups
(lambs versus adults) revealed significantly higher number of fragile bands in adults. Comparison of published data on reciprocal
translocations in sheep with the fragile-site data obtained in this study indicated that the break sites of both phenomena
were correlated. Similarities were also found between fragile sites and breakpoints of evolutionary significance in family
Bovidae. 相似文献
999.
Hossain MS Roback JD Wang F Waller EK 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(10):6892-6902
We have previously shown that amotosalen-treated splenocytes rescued allorecipients from a lethal dose of mouse CMV (MCMV) administered on day 0 in experimental parent C57BL/6-->CB6F1 allogeneic bone marrow transplant. In this study, we investigated the mechanism of antiviral activity of amotosalen-treated donor splenocytes when sublethal MCMV infections were administered 7 days posttransplant. Recipients of 3 x 10(6) untreated splenocytes were used as control. Following MCMV infection, recipients of untreated splenocytes had 40% early mortality due to acute graft-vs-host disease compared with no deaths among recipients of 10 x 10(6) treated splenocytes. However, recipients of both types of donor splenocytes effectively cleared MCMV from their liver. Like the untreated CD8(+) T cells, amotosalen-treated CD8(+) T cells equally retained their in vivo CTL activity against MCMV early peptide-pulsed targets and expressed similar levels of granzyme B within 11 days of infection. In contrast to full donor chimerism in recipients of untreated splenocytes, recipients of amotosalen-treated splenocytes showed mixed chimerism with both donor spleen- and host-derived anti-MCMV CD8(+) T cells in their blood and lymphoid organs, with significantly higher numbers of host-derived CD4(-)CD8(-) (double negative) T cells in the spleens of recipients of treated splenocytes compared with the recipients of untreated splenocytes. Additionally, recipients of amotosalen-treated splenocytes had lower levels of serum IFN-gamma and TNF-alpha in response to MCMV infection compared with untreated recipients. Thus, adoptive immunotherapy with treated T cells is a novel therapeutic approach that facilitates hematopoietic engraftment and permits antiviral immunity of both donor and host T cells without graft-vs-host disease. 相似文献
1000.
Rezaei MA Abdolmaleki P Karami Z Asadabadi EB Sherafat MA Abrishami-Moghaddam H Fadaie M Forouzanfar M 《Journal of theoretical biology》2008,254(4):817-820
In this study, membrane proteins were classified using the information hidden in their sequences. It was achieved by applying the wavelet analysis to the sequences and consequently extracting several features, each of them revealing a proportion of the information content present in the sequence. The resultant features were made normalized and subsequently fed into a cascaded model developed in order to reduce the effect of the existing bias in the dataset, rising from the difference in size of the membrane protein classes. The results indicate an improvement in prediction accuracy of the model in comparison with similar works. The application of the presented model can be extended to other fields of structural biology due to its efficiency, simplicity and flexibility. 相似文献