全文获取类型
收费全文 | 15633篇 |
免费 | 1230篇 |
国内免费 | 7篇 |
专业分类
16870篇 |
出版年
2024年 | 24篇 |
2023年 | 96篇 |
2022年 | 247篇 |
2021年 | 456篇 |
2020年 | 242篇 |
2019年 | 312篇 |
2018年 | 420篇 |
2017年 | 367篇 |
2016年 | 598篇 |
2015年 | 866篇 |
2014年 | 946篇 |
2013年 | 1116篇 |
2012年 | 1434篇 |
2011年 | 1421篇 |
2010年 | 882篇 |
2009年 | 676篇 |
2008年 | 1039篇 |
2007年 | 923篇 |
2006年 | 894篇 |
2005年 | 852篇 |
2004年 | 741篇 |
2003年 | 623篇 |
2002年 | 616篇 |
2001年 | 107篇 |
2000年 | 75篇 |
1999年 | 107篇 |
1998年 | 130篇 |
1997年 | 92篇 |
1996年 | 71篇 |
1995年 | 54篇 |
1994年 | 50篇 |
1993年 | 57篇 |
1992年 | 47篇 |
1991年 | 29篇 |
1990年 | 39篇 |
1989年 | 41篇 |
1988年 | 16篇 |
1987年 | 22篇 |
1986年 | 15篇 |
1985年 | 18篇 |
1984年 | 15篇 |
1983年 | 10篇 |
1982年 | 10篇 |
1981年 | 14篇 |
1980年 | 13篇 |
1979年 | 6篇 |
1978年 | 4篇 |
1977年 | 4篇 |
1975年 | 10篇 |
1974年 | 5篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
241.
The initiation of cytokinesis in the fission yeast Schizosaccharomyces pombe is signalled by the septation initiation network (SIN). Signalling originates from the spindle pole body (SPB), where SIN proteins are anchored by a scaffold composed of cdc11p and sid4p. Cdc11p links the other SIN proteins to sid4p and the SPB. Homologues of cdc11p have been identified in Saccharomyes cerevisiae (Nud1p) and human cells (Centriolin). We have defined functional domains of cdc11p by analysis of deletion mutants. We demonstrate that the C-terminal end of cdc11p is necessary for SPB localisation. We also show that the N-terminal domain is necessary and sufficient for signal transduction, since tethering of this domain to the SPB will substitute for cdc11p in SIN function. 相似文献
242.
Tripodi SA Del Vecchio MT Supuran CT Scozzafava A Gabrielli MG Pastorekova S Rossie R Fasolis G Puccetti L 《Journal of enzyme inhibition and medicinal chemistry》2004,19(3):287-291
Clear renal cell carcinomas (RCC) frequently express carbonic anydrase IX (CA IX) because of non-functional mutation of von Hippel Lindau (VHL) tumor suppressor gene. CA IX is a tumor-associated transmembrane antigen, which catalyzes the extracellular, reversible hydration of carbon dioxide to bicarbonate and proton and thereby contributes to acidification of extracellular milieu. Extracellular acidic pH facilitates tumor growth and progression. CA IX expression is upregulated by Hypoxia Inducible Factor-1 (HIF-1), which is negatively controlled by oxygen via wild type VHL protein and is also regulated by the cell redox state. We investigated the immunohistochemical pattern of distribution of CA IX in a small series (14 cases) of RCCs. CA IX expression was matched with the redox state of RCC, stratifying our series in relation to clinical and histopathological parameters, such as Fuhrman grade, staging, proliferation markers expression, and particularly, the presence of necrosis. Our results show for the first time the existence of a perivascular pattern of CA IX distribution in RCC. We also found a significant relationship between CA IX expression and the presence of necrosis. Tumors with higher CA IX expression exhibited higher degree of necrosis (p < 0.05). Notably, an almost significant relationship between the redox state and CA IX expression was detected in RCC patients with 5 years disease-free survival, most of them showing organ-confined disease. Tumors with lower redox state showed an algebraically higher degree of CA IX expression. On the contrary, tumors with higher redox state exhibited an algebraically lower CA IX expression (p = 0.057). The observed relationship of CA IX expression and necrosis suggests a role for CA IX in RCC. Further investigations are necessary to further establish the role of the redox state in regulation of CA IX expression in RCC. 相似文献
243.
Sargisova Y Pierfederici FM Scirè A Bertoli E Tanfani F Febbraio F Briante R Karapetyan Y Mardanyan S 《Proteins》2004,57(2):302-310
In steroid hydroxylation system in adrenal cortex mitochondria, NADPH-adrenodoxin reductase (AR) and adrenodoxin (Adx) form a short electron-transport chain that transfers electrons from NADPH to cytochromes P-450 through FAD in AR and [2Fe-2S] cluster in Adx. The formation of [AR/Adx] complex is essential for the electron transfer mechanism in which previous studies suggested that AR tryptophan (Trp) residue(s) might be implicated. In this study, we modified AR Trps by N-bromosuccinimide (NBS) and studied AR binding to Adx by a resonant mirror biosensor. Chemical modification of tryptophans caused inhibition of electron transport. The modified protein (AR*) retained the native secondary structure but showed a lower affinity towards Adx with respect to AR. Activity measurements and fluorescence data indicated that one Trp residue of AR may be involved in the electron transferring activity of the protein. Computational analysis of AR and [AR/Adx] complex structures suggested that Trp193 and Trp420 are the residues with the highest probability to undergo NBS-modification. In particular, the modification of Trp420 hampers the correct reorientation of AR* molecule necessary to form the native [AR/Adx] complex that is catalytically essential for electron transfer from FAD in AR to [2Fe-2S] cluster in Adx. The data support an incorrect assembly of [AR*/Adx] complex as the cause of electron transport inhibition. 相似文献
244.
Background
Natively unfolded proteins lack a well defined three dimensional structure but have important biological functions, suggesting a re-assignment of the structure-function paradigm. To assess that a given protein is natively unfolded requires laborious experimental investigations, then reliable sequence-only methods for predicting whether a sequence corresponds to a folded or to an unfolded protein are of interest in fundamental and applicative studies. Many proteins have amino acidic compositions compatible both with the folded and unfolded status, and belong to a twilight zone between order and disorder. This makes difficult a dichotomic classification of protein sequences into folded and natively unfolded ones. In this work we propose an operational method to identify proteins belonging to the twilight zone by combining into a consensus score good performing single predictors of folding. 相似文献245.
Andrea Polle Lars O. Baumbusch Christa Oschinski Monika Eiblmeier Vivian Kuhlenkamp Birgit Vollrath Florian Scholz Heinz Rennenberg 《Oecologia》1999,121(2):149-156
Clones of Norway spruce (Picea abies L.) were grown for several years on an altitudinal gradient (1750 m, 1150 m and 800 m above sea level) to study the effects
of environmental × genetic interactions on growth and foliar metabolites (protein, pigments, antioxidants). Clones at the
tree line showed 4.3-fold lower growth rates and contained 60% less chlorophyll (per gram of dry matter) than those at valley
level. The extent of growth reduction was clone-dependent. The mortality of the clones was low and not altitude-dependent.
At valley level, but not at high altitude, needles of mature spruce trees showed lower pigment and protein concentrations
than clones. In general, antioxidative systems in needles of the mature trees and young clones did not increase with increasing
altitude. Needles of all trees at high altitude showed higher concentrations of dehydroascorbate than at lower altitudes,
indicating higher oxidative stress. In one clone, previously identified as sensitive to acute ozone doses, this increase was
significantly higher and the growth reduction was stronger than in the other genotypes. This clone also displayed a significant
reduction in glutathione reductase activity at high altitude. These results suggest that induction of antioxidative systems
is apparently not a general prerequisite to cope with altitude in clones whose mother plants originated from higher altitudes
(about 650–1100 m above sea level, Hercycnic-Carpathian distribution area), but that the genetic constitution for maintenance
of high antioxidative protection is important for stress compensation at the tree line.
Received: 13 October 1998 / Accepted: 22 June 1999 相似文献
246.
247.
Andrea Hoffmeier Heike Betat Alexander Bluschke Robert Günther Sandy Junghanns Hans-J?rg Hofmann Mario M?rl 《Nucleic acids research》2010,38(13):4436-4447
CCA-adding enzymes are polymerases existing in two distinct enzyme classes that both synthesize the C-C-A triplet at tRNA 3′-ends. Class II enzymes (found in bacteria and eukaryotes) carry a flexible loop in their catalytic core required for switching the specificity of the nucleotide binding pocket from CTP- to ATP-recognition. Despite this important function, the loop sequence varies strongly between individual class II CCA-adding enzymes. To investigate whether this loop operates as a discrete functional entity or whether it depends on the sequence context of the enzyme, we introduced reciprocal loop replacements in several enzymes. Surprisingly, many of these replacements are incompatible with enzymatic activity and inhibit ATP-incorporation. A phylogenetic analysis revealed the existence of conserved loop families. Loop replacements within families did not interfere with enzymatic activity, indicating that the loop function depends on a sequence context specific for individual enzyme families. Accordingly, modeling experiments suggest specific interactions of loop positions with important elements of the protein, forming a lever-like structure. Hence, although being part of the enzyme’s catalytic core, the loop region follows an extraordinary evolutionary path, independent of other highly conserved catalytic core elements, but depending on specific sequence features in the context of the individual enzymes. 相似文献
248.
Andreas Katsiaras Anne B Newman Andrea Kriska Jennifer Brach Shanthi Krishnaswami Eleanor Feingold Stephen B Kritchevsky Rongling Li Tamara B Harris Ann Schwartz Bret H Goodpaster 《Journal of applied physiology》2005,99(1):210-216
We examined the muscle fatigue characteristics in older men and women and determined whether these were related to the size, strength, or quality of muscle. A total of 1,512 men and women aged 70-79 yr from the Health, Aging, and Body Composition Study participated in this study. Muscle cross-sectional area and attenuation were determined with computed tomography. Skeletal muscle fatigue and strength (peak torque) of the knee extensors and flexors were measured using isokinetic dynamometry. Men were more fatigue resistant than women for both knee extension (fatigue index: 70.4 +/- 15.3 vs. 66.9 +/- 14.3%; P < 0.05) and knee flexion (67.9 +/- 16.4 vs. 64.9 +/- 17.6%; P < 0.05). Peak torque and muscle quality (specific torque) were higher in men than women for knee extension (99.6 +/- 28.2 vs. 63.0 +/- 16.8 N x m and 1.62 +/- 0.43 vs. 1.51 +/- 0.39 N x m/cm2; both P < 0.05) and for knee flexion (74.0 +/- 26.4 vs. 49.6 +/- 15.9 N x m and 2.47 +/- 1.29 vs. 2.22 +/- 0.78 N x m/cm2; both P < 0.05). Total work and power output was greater in men compared with women for both the quadriceps (1,353 +/- 451 vs. 832 +/- 264 J and 87.7 +/- 33.5 vs. 53.3 +/- 19.2 W; both P < 0.05) and the hamstrings (741 +/- 244 vs. 510 +/- 141 J and 35.4 +/- 16.0 vs. 23.7 +/- 10.2 W; both P < 0.05). In both genders, the quadriceps was able to perform more work with greater power compared with the hamstrings. Those who were stronger actually had greater fatigue after adjusting for age, race, physical activity, and total body fat. In conclusion, older men were more fatigue resistant than women, although in both men and women greater fatigue was not related to muscle weakness. 相似文献
249.
Muhammad A. Khan Brion Duffy Cesare Gessler Andrea Patocchi 《Molecular breeding : new strategies in plant improvement》2006,17(4):299-306
Fire blight caused by the bacterium Erwinia amylovora is a severe threat to apple and pear orchards worldwide. Apple varieties exhibit a wide range of relative susceptibility/tolerance to fire blight. Although, no monogenic resistance against fire blight has been identified yet, recent evidence indicates the existence of quantitative resistance. Potential sources of fire blight resistance include several wild Malus species and some apple cultivars. F1 progenies of ‘Fiesta’בDiscovery’ were inoculated with the Swiss strain Ea 610 and studied under controlled conditions to identify quantitative trait loci (QTLs) for fire blight resistance. Disease was evaluated at four time points after inoculation. Shoot lesion length and the area under disease progress curve (AUDPC) values were used for QTL analysis. One significant (LOD score of 7.5–8.1, p<0.001) QTL was identified on the linkage group 7 of ‘Fiesta’ (F7). The F7 QTL explained about 37.5–38.6% of the phenotypic variation. 相似文献
250.