全文获取类型
收费全文 | 1153篇 |
免费 | 113篇 |
国内免费 | 101篇 |
出版年
2024年 | 4篇 |
2023年 | 25篇 |
2022年 | 33篇 |
2021年 | 49篇 |
2020年 | 45篇 |
2019年 | 44篇 |
2018年 | 56篇 |
2017年 | 38篇 |
2016年 | 42篇 |
2015年 | 46篇 |
2014年 | 68篇 |
2013年 | 86篇 |
2012年 | 59篇 |
2011年 | 54篇 |
2010年 | 59篇 |
2009年 | 60篇 |
2008年 | 75篇 |
2007年 | 66篇 |
2006年 | 48篇 |
2005年 | 50篇 |
2004年 | 51篇 |
2003年 | 42篇 |
2002年 | 21篇 |
2001年 | 28篇 |
2000年 | 15篇 |
1999年 | 30篇 |
1998年 | 16篇 |
1997年 | 23篇 |
1996年 | 14篇 |
1995年 | 7篇 |
1994年 | 10篇 |
1993年 | 13篇 |
1992年 | 12篇 |
1991年 | 9篇 |
1990年 | 7篇 |
1989年 | 7篇 |
1988年 | 13篇 |
1986年 | 5篇 |
1985年 | 5篇 |
1984年 | 8篇 |
1983年 | 5篇 |
1982年 | 4篇 |
1981年 | 4篇 |
1979年 | 3篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1970年 | 1篇 |
排序方式: 共有1367条查询结果,搜索用时 31 毫秒
111.
Wang J Chu H Zhao H Cheng X Liu Y Jin W Zhao J Liu B Ding Y Ma H 《Molecular and cellular biochemistry》2007,304(1-2):135-142
Previous studies showed that nitricoxide synthase (NOS) and oxidative stress can induce skeletal muscle atrophy in the muscular
dystrophy and inclusion-body myopathy. There is a correlation between NOS and oxidative stress. However, it is not clear,
whether there are some changes of the NOS activity in prolonged alcoholic myopathy (PAM), and whether NOS activity has relation
to amyotrophy of PAM. We established experimental alcoholic myopathy model of rats by prolonged alcohol intake. We found that
there is a reduction in GSH-px (P < 0.05) and an increase of SOD (P < 0.05), MDA (P < 0.05) and iNOS (P < 0.05) in the plantaris of the experimental group by spectrophotometer. In the soleus of the experimental group, except
for MDA showed an increase (P < 0.05), the other enzymes showed no obvious difference (P > 0.05). The immunohistochemistry results showed that there was obvious expression of iNOS in the cytoplasm of plantaris
in the experimental group and there was no expression of iNOS in the control group. There was a decrease of nNOS expression
on the membranes of the plantaris cells in the experimental group by immunofluorescence. Meanwhile, we found the expression
of nNOS in some cytoplasm. Our results suggested that NOS might be an important factor during the development of PAM. We could
infer that there are some disturbances with regard to output and scavenging of free radical in PAM. Alcohol can induce the
oxidative stress reaction and further result in imbalance of the oxidant-antioxidant status in the organism.
Haiying Chu is the co-first author. 相似文献
112.
Mikhail L. Antonkine Estelle M. Maes Christoph Breitenstein Christopher J. Falzone Carolyn Lubner John H. Golbeck 《BBA》2007,1767(6):712-724
Chemical rescue of site-modified amino acids using externally supplied organic molecules represents a powerful method to investigate structure-function relationships in proteins. Here we provide definitive evidence that aryl and alkyl thiolates, reagents typically used for in vitro iron-sulfur cluster reconstitutions, serve as rescue ligands to a site-specifically modified [4Fe-4S]1+,2+ cluster in PsaC, a bacterial dicluster ferredoxin-like subunit of Photosystem I. PsaC binds two low-potential [4Fe-4S]1+,2+ clusters termed FA and FB. In the C13G/C33S variant of PsaC, glycine has replaced cysteine at position 13 creating a protein that is missing one of the ligating amino acids to iron-sulfur cluster FB. Using a variety of analytical techniques, including non-heme iron and acid-labile sulfur assays, and EPR, resonance Raman, and Mössbauer spectroscopies, we showed that the C13G/C33S variant of PsaC binds two [4Fe-4S]1+,2+ clusters, despite the absence of one of the biological ligands. 19F NMR spectroscopy indicated that the external thiolate replaces cysteine 13 as a substitute ligand to the FB cluster. The finding that site-modified [4Fe-4S]1+,2+ clusters can be chemically rescued with external thiolates opens new opportunities for modulating their properties in proteins. In particular, it provides a mechanism to attach an additional electron transfer cofactor to the protein via a bound, external ligand. 相似文献
113.
The Lake Taihu drainage basin is an economically developed area with some of the highest population densities in China. The
lake has deteriorated due to ecological destruction and eutrophication. Three short sediment cores from eastern, northeastern
and southwestern Lake Taihu were collected. Total organic carbon (TOC), total nitrogen (TN), pigments, elements and particle
size were analyzed for the purpose of understanding past trophic status and pollution levels. Sedimentation rates were based
on 137Cs or 210Pb methods. Results indicated that sediment particle size became coarser since the 1920s, and the lake was contaminated by
heavy metals, such as Cu and Zn, since the 1970s. A remarkable increase in eutrophication since the 1980s due to increased
loading of untreated effluents from industry, agriculture and urbanization is reflected by total organic carbon, total nitrogen
and pigments in the studied cores. However the onset times of eutrophication in different parts of Lake Taihu were not synchronous. 相似文献
114.
Hsu EC Lin YC Hung CS Huang CJ Lee MY Yang SC Ting LP 《Journal of biomedical science》2007,14(6):731-744
Summary Protein-tyrosine phosphatase PTPN3 is a membrane-associated non-receptor protein-tyrosine phosphatase. PTPN3 contains a N-terminal
FERM domain, a middle PDZ domain, and a C-terminal phosphatase domain. Upon co-expression of PTPN3, the level of human hepatitis
B viral (HBV) RNAs, 3.5 kb, 2.4/2.1 kb, and 0.7 kb transcribed from a replicating HBV expression plasmid is significantly
reduced in human hepatoma HuH-7 cells. When the expression of endogenous PTPN3 protein is diminished by specific small interfering
RNA, the expression of HBV genes is enhanced, indicating that the endogenous PTPN3 indeed plays a suppressive role on HBV
gene expression. PTPN3 can interact with HBV core protein. The interaction is mediated via the PDZ domain of PTPN3 and the
carboxyl-terminal last four amino acids of core. Either deletion of PDZ domain of PTPN3 or substitution of PDZ ligand in core
has no effect on PTPN3-mediated suppression. These results clearly show that the interaction of PTPN3 with core is not required
for PTPN3 suppressive effect. Mutation of 359serine and 835serine of 14-3-3β binding sites to alanine, which slightly reduces the interaction with 14-3-3β, does not influence the PTPN3
effect. In contrast, mutation of the invariant 842cysteine residue in phosphatase domain to serine, which makes the phosphatase activity inactive, does not change its subcellular
localization and interaction with core or 14-3-3β, but completely abolishes PTPN3-mediated suppression. Furthermore, deletion
of FERM domain does not affect the phosphatase activity or interaction with 14-3-3β, but changes the subcellular localization
from cytoskeleton-membrane interface to cytoplasm and nucleus, abolishes binding to core, and diminishes the PTPN3 effect
on HBV gene expression. Taken together, these results demonstrate that the phosphatase activity and FERM domain of PTPN3 are
essential for its suppression of HBV gene expression.
En-Chi Hsu, Yen-Cheng Lin have equal contributions to this work. 相似文献
115.
Functional analysis of cauliflower mosaic virus 35S promoter: re-evaluation of the role of subdomains B5, B4 and B2 in promoter activity 总被引:3,自引:0,他引:3
Bhullar S Datta S Advani S Chakravarthy S Gautam T Pental D Burma PK 《Plant biotechnology journal》2007,5(6):696-708
The cauliflower mosaic virus 35S (35S) promoter is used extensively for transgene expression in plants. The promoter has been delineated into different subdomains based on deletion analysis and gain-of-function studies. However, cis -elements important for promoter activity have been identified only in the domains B1 ( as-2 element), A1 ( as-1 element) and minimal promoter (TATA box). No cis -elements have been described in subdomains B2–B5, although these are reported to be important for the overall activity of the 35S promoter. We have re-evaluated the contribution of three of these subdomains, namely B5, B4 and B2, to 35S promoter activity by developing several modified promoters. The analysis of β-glucuronidase gene expression driven by the modified promoters in different tissues of primary transgenic tobacco lines, as well as in seedlings of the T1 generation, revealed new facets about the functional organization of the 35S promoter. This study suggests that: (i) the 35S promoter truncated up to –301 functions in a similar manner to the –343 (full-length) 35S promoter; (ii) the Dof core and I-box core observed in the subdomain B4 are important for 35S promoter activity; and (iii) the subdomain B2 is essential for maintaining an appropriate distance between the proximal and distal regions of the 35S promoter. These observations will aid in the development of functional synthetic 35S promoters with decreased sequence homology. Such promoters can be used to drive multiple transgenes without evoking promoter homology-based gene silencing when attempting gene stacking. 相似文献
116.
Brittany L. Wagler Rachel A. Smiley Alyson B. Courtemanch Gregory Anderson Daryl Lutz Doug McWhirter Doug Brimeyer Patrick Hnilicka Cody P. Massing David W. German Thomas R. Stephenson Kevin L. Monteith 《The Journal of wildlife management》2022,86(3):e22181
Wildlife capture, and the data collection associated with it, has led to major advancements in ecology that are integral to decision making pertaining to wildlife conservation. Capturing wildlife, however, can cause lethal and non-lethal risks to animals. Understanding the factors that contribute to the level of risk involved in wildlife capture is therefore important for the development and implementation of the safest and most effective methodologies. We used data from 736 animal captures of 389 individuals for 2 subspecies of female bighorn sheep (Rocky Mountain bighorn [Ovis canadensis canadensis], Sierra Nevada bighorn sheep [O. c. sierrae]) in Wyoming and California, USA, in 2002–2020 to evaluate the degree and extent of time that capture via helicopter net-gunning affects survival. We compared pre- and post-capture survival during a 10-week window centered on a capture event, and post-capture survival between captured animals and animals that were monitored but not captured during the 10-week window. Additionally, we evaluated the effects of handling techniques (number of times captured, season of capture event, handling time, chase time, and body temp) and biological factors (age and nutritional condition) on probability of capture mortality. Mean daily survival was 0.9992 during a 5-week pre-capture window, dropped to 0.9864 on the day of capture, and rebounded within 3 days of capture to pre-capture levels and that of sheep that were not captured. Overall, direct mortality resulting from capture was 1.36%, with 0.54% mortality occurring within the 3 days following a capture event for an overall 1.90% capture-related mortality. The only handling and biological metrics that influenced the probability of capture mortality were rectal temperature and nutritional condition; high initial rectal temperatures and poor body condition were associated with increased risk of mortality in the days following capture. Overall, helicopter net-gunning imposed low and short-term risk to survival of female bighorn sheep. To reduce bias in survival estimates, we recommend using a 3-day censorship window for post-capture mortalities as opposed to the common practice of a 2–5-week censor window. Helicopter net-gunning, including annual or seasonal recaptures, remains an effective and comparatively safe technique for capture and associated data collection of bighorn sheep. 相似文献
117.
Zanlin Yu Nurit Livnat-Levanon Oded Kleifeld Wissam Mansour Mark?A. Nakasone Carlos?A. Castaneda Emma?K. Dixon David Fushman Noa Reis Elah Pick Michael?H. Glickman 《Bioscience reports》2015,35(3)
26S proteasome, a major regulatory protease in eukaryotes, consists of a 20S proteolytic core particle (CP) capped by a 19S regulatory particle (RP). The 19S RP is divisible into base and lid sub-complexes. Even within the lid, subunits have been demarcated into two modules: module 1 (Rpn5, Rpn6, Rpn8, Rpn9 and Rpn11), which interacts with both CP and base sub-complexes and module 2 (Rpn3, Rpn7, Rpn12 and Rpn15) that is attached mainly to module 1. We now show that suppression of RPN11 expression halted lid assembly yet enabled the base and 20S CP to pre-assemble and form a base-CP. A key role for Regulatory particle non-ATPase 11 (Rpn11) in bridging lid module 1 and module 2 subunits together is inferred from observing defective proteasomes in rpn11–m1, a mutant expressing a truncated form of Rpn11 and displaying mitochondrial phenotypes. An incomplete lid made up of five module 1 subunits attached to base-CP was identified in proteasomes isolated from this mutant. Re-introducing the C-terminal portion of Rpn11 enabled recruitment of missing module 2 subunits. In vitro, module 1 was reconstituted stepwise, initiated by Rpn11–Rpn8 heterodimerization. Upon recruitment of Rpn6, the module 1 intermediate was competent to lock into base-CP and reconstitute an incomplete 26S proteasome. Thus, base-CP can serve as a platform for gradual incorporation of lid, along a proteasome assembly pathway. Identification of proteasome intermediates and reconstitution of minimal functional units should clarify aspects of the inner workings of this machine and how multiple catalytic processes are synchronized within the 26S proteasome holoenzymes. 相似文献
118.
On the effect of hydrostatic pressure on the conformational stability of globular proteins
下载免费PDF全文
![点击此处可从《Biopolymers》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Giuseppe Graziano 《Biopolymers》2015,103(12):711-718
The model developed for cold denaturation (Graziano, PCCP 2010, 12, 14245‐14252) is extended to rationalize the dependence of protein conformational stability upon hydrostatic pressure, at room temperature. A pressure− volume work is associated with the process of cavity creation for the need to enlarge the liquid volume against hydrostatic pressure. This contribution destabilizes the native state that has a molecular volume slightly larger than the denatured state due to voids existing in the protein core. Therefore, there is a hydrostatic pressure value at which the pressure−volume contribution plus the conformational entropy loss of the polypeptide chain are able to overwhelm the stabilizing gain in translational entropy of water molecules, due to the decrease in water accessible surface area upon folding, causing denaturation. © 2015 Wiley Periodicals, Inc. Biopolymers 103: 711–718, 2015. 相似文献
119.
Non‐territorial Macaques Can Range Like Territorial Gibbons When Partially Provisioned With Food
下载免费PDF全文
![点击此处可从《Biotropica》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Juan Manuel José‐Domínguez Marie‐Claude Huynen Carmen J. García Aurélie Albert‐Daviaud Norberto Asensio 《Biotropica》2015,47(6):733-744
Human food supplementation can affect components of animal socioecology by altering the abundance and distribution of available food. We studied the effect of food supplementation by comparing the ranging patterns and intergroup interactions of two groups of northern pigtailed macaques (Macaca leonina), a non‐territorial primate species. One group was partially reliant on food provisioning, whereas the other group foraged wild food. We also compared the macaques’ movement with that of a group of white‐handed gibbons (Hylobates lar), a territorial species inhabiting the same site. Home range, core area, and daily path lengths were significantly smaller for the semi‐provisioned group than for the wild‐feeding group. In contrast to wild‐feeding macaques, supplemented macaques showed higher fidelity to home range, core area, and particularly to the region where human food was most accessible and abundant. The relationship of daily path length and home range indicated a low defendability index for wild‐feeding macaques; the higher index for the semi‐provisioned group was consistent with the territorial pattern found in gibbons. Semi‐provisioned macaques showed further traits of territoriality with aggression during intergroup encounters. These findings indicate that human modification of food availability can significantly affect movement patterns and intergroup competition in macaques. The observed ranging dynamics related to food provisioning may decrease the efficiency of macaques as seed dispersers and increase predation on their home range, and thus have important consequences for plant regeneration and animal diversity. 相似文献
120.
High-density hardwood trees with large diameters have been found to damage manually operated increment borers, thus limiting their use in the tropics. Therefore, we herein report a new, low-cost gasoline-powered sampling system for high-density tropical hardwood trees with large diameters. This system provides increment cores 15 mm in diameter and up to 1.35 m in length, allowing minimally invasive sampling of tropical hardwood tree species, which, up to the present, could not be collected by conventional 5 or 10 mm increment borers. This system provides a single core sample with ample amount of wood for multidisciplinary analyses, including ring width, stable isotope and wood anatomical measurements. The borer never gets stuck inside stems, even in hollowed trees, cores will never twist during coring, and the gasoline drill gives ample flexibility in the field. It is anticipated that the dendrochronological community will find our technique very useful in the pursuit of tropical tree ring research. 相似文献