全文获取类型
收费全文 | 1483篇 |
免费 | 88篇 |
国内免费 | 4篇 |
专业分类
1575篇 |
出版年
2024年 | 2篇 |
2023年 | 14篇 |
2022年 | 26篇 |
2021年 | 35篇 |
2020年 | 25篇 |
2019年 | 27篇 |
2018年 | 39篇 |
2017年 | 37篇 |
2016年 | 48篇 |
2015年 | 71篇 |
2014年 | 88篇 |
2013年 | 106篇 |
2012年 | 141篇 |
2011年 | 115篇 |
2010年 | 79篇 |
2009年 | 79篇 |
2008年 | 94篇 |
2007年 | 107篇 |
2006年 | 88篇 |
2005年 | 70篇 |
2004年 | 54篇 |
2003年 | 60篇 |
2002年 | 49篇 |
2001年 | 5篇 |
2000年 | 5篇 |
1999年 | 4篇 |
1998年 | 8篇 |
1997年 | 6篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 3篇 |
1991年 | 7篇 |
1990年 | 11篇 |
1989年 | 4篇 |
1988年 | 4篇 |
1985年 | 7篇 |
1984年 | 4篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1981年 | 2篇 |
1980年 | 7篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1976年 | 5篇 |
1975年 | 5篇 |
1974年 | 3篇 |
1973年 | 3篇 |
1972年 | 2篇 |
排序方式: 共有1575条查询结果,搜索用时 12 毫秒
991.
Feed-forward and feed-backward amplification model from cochlear cytoarchitecture: an interspecies comparison 总被引:1,自引:0,他引:1
The high sensitivity and wide bandwidth of mammalian hearing are thought to derive from an active process involving the somatic and hair-bundle motility of the thousands of outer hair cells uniquely found in mammalian cochleae. To better understand this, a biophysical three-dimensional cochlear fluid model was developed for gerbil, chinchilla, cat, and human, featuring an active “push-pull” cochlear amplifier mechanism based on the cytoarchitecture of the organ of Corti and using the time-averaged Lagrangian method. Cochlear responses are simulated and compared with in vivo physiological measurements for the basilar membrane (BM) velocity, VBM, frequency tuning of the BM vibration, and Q10 values representing the sharpness of the cochlear tuning curves. The VBM simulation results for gerbil and chinchilla are consistent with in vivo cochlea measurements. Simulated mechanical tuning curves based on maintaining a constant VBM value agree with neural-tuning threshold measurements better than those based on a constant displacement value, which implies that the inner hair cells are more sensitive to VBM than to BM displacement. The Q10 values of the VBM tuning curve agree well with those of cochlear neurons across species, and appear to be related in part to the width of the basilar membrane. 相似文献
992.
993.
Avian paramyxovirus serotype 2 (APMV-2) is one of the nine serotypes of APMV, which infect a wide variety of avian species around the world. In this study, we constructed a reverse genetics system for recovery of infectious recombinant APMV-2 strain Yucaipa (APMV-2/Yuc) from cloned cDNA. The rescued recombinant virus (rAPMV-2) resembled the biological virus in growth properties in vitro and in pathogenicity in vivo. The reverse genetics system was used to analyze the role of the cleavage site of the fusion (F) protein in viral replication and pathogenesis. The cleavage site of APMV-2/Yuc (KPASR↓F) contains only a single basic residue (position -1) that matches the preferred furin cleavage site [RX(K/R)R↓]. (Underlining indicates the basic amino acids at the F protein cleavage site, and the arrow indicates the site of cleavage.) Contrary to what would be expected for this cleavage sequence, APMV-2 does not require, and is not augmented by, exogenous protease supplementation for growth in cell culture. However, it does not form syncytia, and the virus is avirulent in chickens. A total of 12 APMV-2 mutants with F protein cleavage site sequences derived from APMV serotypes 1 to 9 were generated. These sites contain from 1 to 5 basic residues. Whereas a number of these cleavage sites are associated with protease dependence and lack of syncytium formation in their respective native viruses, when transferred into the APMV-2 backbone, all of them conferred protease independence, syncytium formation, and increased replication in cell culture. Examination of selected mutants during a pulse-chase experiment demonstrated an increase in F protein cleavage compared to that for wild-type APMV-2. Despite the gains in cleavability, replication, and syncytium formation, analysis of viral pathogenicity in 9-day-old embryonated chicken eggs, 1-day-old chicks, and 2-week-old chickens showed that the F protein cleavage site mutants did not exhibit increased pathogenicity and remained avirulent. These results imply that structural features in addition to the cleavage site play a major role in the cleavability of the F protein and the activity of the cleaved protein. Furthermore, cleavage of the F protein is not a determinant of APMV-2 pathogenicity in chickens. 相似文献
994.
Toll-like receptors (TLR) -7 and -8 are thought to play an important role in immune activation processes underlying the pathophysiology of HIV and several clinically important autoimmune diseases. Based on our earlier findings of TLR7-antagonistic activity in a 3H imidazoquinoline, we sought to examine a pilot library of 3H imidazoquinolines for dual TLR7/8 antagonists, since they remain a poorly explored chemotype. 2D-NOE experiments were employed to unequivocally characterize the compounds. A quinolinium compound 12, bearing p-methoxybenzyl substituents on N3 and N5 positions was identified as a lead. Compound 12 was found to inhibit both TLR7 and TLR8 at low micromolar concentrations. Our preliminary results suggest that alkylation with electron-rich substituents on the quinoline N5, or conversely, elimination of the fixed charge of the resultant quaternary amine on the quinolinium may yield more active compounds. 相似文献
995.
996.
Jihoon Ryu Zeenia Kaul A-Rum Yoon Ye Liu Tomoko Yaguchi Youjin Na Hyo Min Ahn Ran Gao Il-Kyu Choi Chae-Ok Yun Sunil C. Kaul Renu Wadhwa 《The Journal of biological chemistry》2014,289(36):24832-24844
The Hsp70 family protein mortalin is an essential chaperone that is frequently enriched in cancer cells and exists in various subcellular sites, including the mitochondrion, plasma membrane, endoplasmic reticulum, and cytosol. Although the molecular mechanisms underlying its multiple subcellular localizations are not yet clear, their functional significance has been revealed by several studies. In this study, we examined the nuclear fractions of human cells and found that the malignantly transformed cells have more mortalin than the normal cells. We then generated a mortalin mutant that lacked a mitochondrial targeting signal peptide. It was largely localized in the nucleus, and, hence, is called nuclear mortalin (mot-N). Functional characterization of mot-N revealed that it efficiently protects cancer cells against endogenous and exogenous oxidative stress. Furthermore, compared with the full-length mortalin overexpressing cancer cells, mot-N derivatives showed increased malignant properties, including higher proliferation rate, colony forming efficacy, motility, and tumor forming capacity both in in vitro and in vivo assays. We demonstrate that mot-N promotes carcinogenesis and cancer cell metastasis by inactivation of tumor suppressor protein p53 functions and by interaction and functional activation of telomerase and heterogeneous ribonucleoprotein K (hnRNP-K) proteins. 相似文献
997.
Gene expression can be altered by small molecules that target DNA; sequence as well as shape selectivities are both extremely important for DNA recognition by intercalating and groove‐binding ligands. We have characterized a carbohydrate scaffold (1) exhibiting DNA “shape readout” properties. Thermodynamic studies with 1 and model duplex DNAs demonstrate the molecule's high affinity and selectivity towards B* form (continuous AT‐rich) DNA. Isothermal titration calorimetry (ITC), circular dichroism (CD) titration, ultraviolet (UV) thermal denaturation, and Differential Scanning Calorimetry were used to characterize the binding of 1 with a B* form AT‐rich DNA duplex d[5′‐G2A6T6C2‐3′]. The binding constant was determined using ITC at various temperatures, salt concentrations, and pH. ITC titrations were fit using a two‐binding site model. The first binding event was shown to have a 1:1 binding stoichiometry and was predominantly entropy‐driven with a binding constant of approximately 108 M?1. ITC‐derived binding enthalpies were used to obtain the binding‐induced change in heat capacity (ΔCp) of ?225 ± 19 cal/mol·K. The ionic strength dependence of the binding constant indicated a significant electrolytic contribution in ligand:DNA binding, with approximately four to five ion pairs involved in binding. Ligand 1 displayed a significantly higher affinity towards AT‐tract DNA over sequences containing GC inserts, and binding experiments revealed the order of binding affinity for 1 with DNA duplexes: contiguous B* form AT‐rich DNA (d[5′‐G2A6T6C2‐3′]) >B form alternate AT‐rich DNA (d[5′‐G2(AT)6C2‐3′]) > A form GC‐rich DNA (d[5′‐A2G6C6T2‐3′]), demonstrating the preference of ligand 1 for B* form DNA. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 720–732, 2014. 相似文献
998.
Antisense RNA ribozymes have intrinsic endonucleolytic activity to effect cleavage of the target RNA. However, this activity in vivo is often controlled by the dominance of antisense or other double-stranded RNA mechanism. In this work, we demonstrate the in planta activity of a hammerhead ribozyme designed to target rep-mRNA of a phytopathogen Mungbean Yellow Mosaic India virus (MYMIV) as an antiviral agent. We also found RNA-silencing is induced on introduction of catalytically active as well as inactive ribozymes. Using RNA-silencing suppressors (RSS), we demonstrate that the endonucleolytic activity of ribozymes is a true phenomenon, even while a mutated version may demonstrate a similar down-regulation of the target RNA. This helps to ease the confusion over the action mechanism of ribozymes in vivo. 相似文献
999.
Keshavamurthy Vinay Geeti Khullar Savita Yadav Amrinder J. Kanwar Uma N. Saikia M. R. Shivaprakash Arunaloke Chakrabarti Sunil Dogra 《Mycopathologia》2014,177(3-4):179-185
Cutaneous aspergillosis is a common systemic mycosis affecting immunosuppressed patients. Here, we describe a novel morphological type of cutaneous aspergillosis in a young immunocompetent woman who presented with a chronic history of multiple nodules and discharging sinuses over left side of the face, mimicking cervicofacial actinomycosis. Skin biopsy showed granulomatous inflammation, and of septate fungal hyphae with acute-angled branching, morphologically resembling Aspergillus. This was confirmed on fungal culture as Aspergillus flavus. 相似文献
1000.
Genetic diversity of 70 isolates of Fusarium oxysporum f. sp. ciceris originated from various states of India representing eight races causing wilt in chickpea (Cicer arietinum) was analyzed using translation elongation factor-1α (TEF-1α), β-tubulin, and internal transcribed spacer (ITS) gene regions. TEF-1α, β-tubulin, and ITS gene-specific markers produced ~720-, ~500-, and ~550-bp amplicons, respectively, in all the isolates of the pathogen. A phylogenetic tree constructed from the sequences generated in the present study along with the sequences of foreign isolates of Fusarium species available in NCBI database sharing more than 90 % nucleotide sequence similarity grouped the isolates into two major clusters. Most of the isolates of the present study showed more or less similar grouping pattern in case of the three gene sequences. Each group had the isolates representing different races as well as place of origin indicating low level of diversity among the isolates in respect of these gene sequences. Except TEF-1α, the groups generated by β-tubulin and ITS gene sequences did not correspond to the state of origin and races of the pathogen. However, the groups of TEF-1α partially corresponded to the place of origin as well as races of the pathogen. The isolates did not show any race-specific grouping patterns; however, most of the isolates representing race 1 clustered separately. 相似文献