全文获取类型
收费全文 | 5217篇 |
免费 | 432篇 |
国内免费 | 1篇 |
出版年
2023年 | 29篇 |
2022年 | 62篇 |
2021年 | 110篇 |
2020年 | 79篇 |
2019年 | 114篇 |
2018年 | 134篇 |
2017年 | 120篇 |
2016年 | 184篇 |
2015年 | 234篇 |
2014年 | 267篇 |
2013年 | 342篇 |
2012年 | 331篇 |
2011年 | 322篇 |
2010年 | 256篇 |
2009年 | 199篇 |
2008年 | 240篇 |
2007年 | 286篇 |
2006年 | 228篇 |
2005年 | 222篇 |
2004年 | 210篇 |
2003年 | 198篇 |
2002年 | 165篇 |
2001年 | 101篇 |
2000年 | 99篇 |
1999年 | 95篇 |
1998年 | 53篇 |
1997年 | 52篇 |
1996年 | 40篇 |
1995年 | 42篇 |
1994年 | 39篇 |
1993年 | 38篇 |
1992年 | 61篇 |
1991年 | 57篇 |
1990年 | 33篇 |
1989年 | 65篇 |
1988年 | 45篇 |
1987年 | 44篇 |
1986年 | 40篇 |
1985年 | 33篇 |
1984年 | 27篇 |
1983年 | 27篇 |
1982年 | 22篇 |
1981年 | 26篇 |
1980年 | 22篇 |
1979年 | 26篇 |
1978年 | 16篇 |
1977年 | 16篇 |
1974年 | 17篇 |
1972年 | 15篇 |
1970年 | 15篇 |
排序方式: 共有5650条查询结果,搜索用时 265 毫秒
961.
962.
del Pozo Yauner L Ortiz E Sánchez R Sánchez-López R Güereca L Murphy CL Allen A Wall JS Fernández-Velasco DA Solomon A Becerril B 《Proteins》2008,72(2):684-692
Light chain-associated amyloidosis is a fatal disease characterized by the aggregation and pathologic deposition of monoclonal light chain-related fragments as amyloid fibrils in organs or tissues throughout the body. Notably, it has been observed that proteins encoded by the lambda variable light chain (V(L)) gene segment 6a are invariably associated with amyloid deposition; however, the contribution of the gene to this phenomenon has not been established. In this regard, we have determined the thermodynamic stability and kinetics of in vitro fibrillogenesis of a recombinant (r) V(L) protein, designated 6aJL2, which contains the predicted sequences encoded by the 6a and JL2 germline genes. Additionally, we studied a 6a mutant (6aJL2-Arg25Gly), that is present in approximately 25% of all amyloid-associated lambda6 light chains. Remarkably, the wild-type 6aJL2 protein was more stable than were all known amyloidogenic kappa and lambda light chains for which stability parameters are available; more importantly, it was even more so (and less fibrillogenic) than the only clinically proven nonamyloidogenic lambda6 protein, Jto. Conversely, the mutated 6aJL2-R25G molecule was considerably less stable and more fibrillogenic than was the native 6aJL2. Our data indicate that the propensity of lambda6 light chains to form amyloid can not be attributed to thermodynamic instability of the germline-encoded Vlambda6 domain, but rather, is dependent on sequence alterations that render such proteins amyloidogenic. 相似文献
963.
964.
Karin A. Riske Tatiane P. Sudbrack Adjaci F. Uchoa Carlos M. Marques Rosangela Itri 《Biophysical journal》2009,97(5):1362-1370
We have synthesized the amphiphile photosensitizer PE-porph consisting of a porphyrin bound to a lipid headgroup. We studied by optical microscopy the response to light irradiation of giant unilamellar vesicles of mixtures of unsaturated phosphatidylcholine lipids and PE-porph. In this configuration, singlet oxygen is produced at the bilayer surface by the anchored porphyrin. Under irradiation, the PE-porph decorated giant unilamellar vesicles exhibit a rapid increase in surface area with concomitant morphological changes. We quantify the surface area increase of the bilayers as a function of time and photosensitizer molar fraction. We attribute this expansion to hydroperoxide formation by the reaction of the singlet oxygen with the unsaturated bonds. Considering data from numeric simulations of relative area increase per phospholipid oxidized (15%), we measure the efficiency of the oxidative reactions. We conclude that for every 270 singlet oxygen molecules produced by the layer of anchored porphyrins, one eventually reacts to generate a hydroperoxide species. Remarkably, the integrity of the membrane is preserved in the full experimental range explored here, up to a hydroperoxide content of 60%, inducing an 8% relative area expansion. 相似文献
965.
A.M. Marqués A. Pinazo F.J. Aranda A. Ortiz M.J. Espuny 《Chemistry and physics of lipids》2009,158(2):110-726
This study analyzed the chemical and physical properties of a biosurfactant synthesized by Rhodococcus sp. 51T7. The biosurfactant was a trehalose tetraester (THL) consisting of six components: one major and five minor. The hydrophobic moieties ranged in size from 9 to 11 carbons. The critical micelle concentration (CMC) was 0.037 g L−1 and the interfacial tension against hexadecane was 5 mN m−1. At pH 7.4 the glycolipid CMC/critical aggregation concentration (CAC) was 0.05 g L−1 and at pH 4 it was 0.034 g L−1. A phase diagram revealed effective emulsification with water and paraffin or isopropyl myristate. A composition of 11.3-7.5-81.8 (isopropyl myristate-THL-W) was stable for at least 3 months. The HLB was 11 and the phase behaviour of the glycolipid revealed the formation of lamellar and hexagonal liquid-crystalline textures. 相似文献
966.
Marcia R. Cominetti Ana Carolina B.M. Martin Juliana U. Ribeiro Ibtissem Djaafri Françoise Fauvel-Lafève Michel Crépin Heloisa S. Selistre-de-Araujo 《Biochimie》2009
This work aimed to investigate the role of the disintegrin domain of the human ADAM9 (ADAM9D) on the adhesion of breast tumor cells and platelets to collagen I, in a dynamic flow assay to simulate in vivo shear conditions. Recombinant ADAM9D was able to support tumor cell adhesion through binding to the β1 integrin subunit and also to inhibit the invasion through matrigel in vitro. In a dynamic flow assay ADAM9D inhibited about 75% and 65% of MDA-MB-231 tumor cells and platelet adhesion to collagen I, respectively. In addition, it was demonstrated that αVβ3 integrin is new interacting partner for ADAM9D. In conclusion, these results suggest a role for the disintegrin domain of ADAM9 in the metastatic process. Also, ADAM9D may be a tool for investigating the role of ADAMs in metastasis and cancer progression and for the design of selective inhibitors against the adhesion and extravasation of cancer cells. 相似文献
967.
María Ángeles Ortiz Karin Tremetsberger Tod F. Stuessy Anass Terrab Juan L. García-Castaño Salvador Talavera 《Journal of Biogeography》2009,36(7):1384-1397
Aim To analyse phylogeographic patterns in the four species of Hypochaeris sect. Hypochaeris , evaluating possible areas of origin and the microevolutionary processes that have shaped their morphology, genetics and distribution.
Location Western Mediterranean area.
Methods We applied amplified fragment length polymorphism (AFLP) markers to a total of 494 individuals belonging to 82 populations of Hypochaeris arachnoidea , H. glabra , H. radicata and H. salzmanniana to determine population structure.
Results Populations with the largest proportion of private and rare AFLP fragments were found in Morocco. This region was consequently inferred to be the ancestral area for H. arachnoidea , H. glabra , H. radicata and H. salzmanniana . The Guadalquivir River (southern Spain) was inferred to be an effective dispersal barrier for H. glabra and H. radicata. The Strait of Gibraltar was inferred to be a somewhat weaker barrier than the Guadalquivir River for H. radicata and a much weaker barrier for H. glabra . The main barrier for H. salzmanniana coincides with the extension of the Rif Mountains to the Atlantic coast in Morocco, and the Strait of Gibraltar is a much weaker barrier for this species. Hypochaeris arachnoidea appears to have originated in the Atlas Mountains.
Main conclusions The highest levels of genetic variation in La Mamora forest ( H. glabra and H. salzmanniana ) or the adjacent central Middle Atlas ( H. arachnoidea and H. radicata ) in Morocco suggest that these areas were a centre of origin of Hypochaeris sect. Hypochaeris . All three potential barriers – the Guadalquivir River, the Strait of Gibraltar, and the Rif Mountains – have been important in shaping genetic diversity in species of section Hypochaeris . 相似文献
Location Western Mediterranean area.
Methods We applied amplified fragment length polymorphism (AFLP) markers to a total of 494 individuals belonging to 82 populations of Hypochaeris arachnoidea , H. glabra , H. radicata and H. salzmanniana to determine population structure.
Results Populations with the largest proportion of private and rare AFLP fragments were found in Morocco. This region was consequently inferred to be the ancestral area for H. arachnoidea , H. glabra , H. radicata and H. salzmanniana . The Guadalquivir River (southern Spain) was inferred to be an effective dispersal barrier for H. glabra and H. radicata. The Strait of Gibraltar was inferred to be a somewhat weaker barrier than the Guadalquivir River for H. radicata and a much weaker barrier for H. glabra . The main barrier for H. salzmanniana coincides with the extension of the Rif Mountains to the Atlantic coast in Morocco, and the Strait of Gibraltar is a much weaker barrier for this species. Hypochaeris arachnoidea appears to have originated in the Atlas Mountains.
Main conclusions The highest levels of genetic variation in La Mamora forest ( H. glabra and H. salzmanniana ) or the adjacent central Middle Atlas ( H. arachnoidea and H. radicata ) in Morocco suggest that these areas were a centre of origin of Hypochaeris sect. Hypochaeris . All three potential barriers – the Guadalquivir River, the Strait of Gibraltar, and the Rif Mountains – have been important in shaping genetic diversity in species of section Hypochaeris . 相似文献
968.
969.
Manuel Stach Maria Knapp Jennifer Ortiz Thomas Ruppert Johannes Lechner 《The EMBO journal》2009,28(8):1099-1110
The protein kinase Mps1 is, among others, essential for the spindle assembly checkpoint (SAC). We found that Saccharomyces cerevisiae Mps1 interacts physically with the N-terminal domain of Ndc80 (Ndc801−257), a constituent of the Ndc80 kinetochore complex. Furthermore, Mps1 effectively phosphorylates Ndc801−257 in vitro and facilitates Ndc80 phosphorylation in vivo. Mutating 14 of the phosphorylation sites to alanine results in compromised checkpoint signalling upon nocodazole treatment of mutants. Mutating the identical sites to aspartate (to simulate constitutive phosphorylation) causes a metaphase arrest with wild-type-like bipolar kinetochore–microtubule attachment. This arrest is due to a constitutively active SAC and consequently the inviable aspartate mutant can be rescued by disrupting SAC signalling. Therefore, we conclude that a putative Mps1-dependent phosphorylation of Ndc80 is important for SAC activation at kinetochores. 相似文献
970.
The SenS/SenR system of Streptomyces reticuli regulates the expression of the redox regulator FurS, the catalase-peroxidase CpeB and the heme-binding protein HbpS. SenS/SenR
is also proposed to participate in sensing redox changes, mediated by HbpS. Here, we show in vitro that heme-free HbpS represses
the autokinase activity of SenS; whereas hemin-treated HbpS considerably enhances SenS autophosphorylation under redox conditions
using either H2O2 or DTT. The presence of iron ions alone or in combination with H2O2 or DTT also leads to significantly increased phosphorylation levels of SenS. Further comparative physiological studies using
the S. reticuli WT, a S. reticuli
hbpS mutant and a S. reticuli
senS-senR mutant corroborates the importance of HbpS and the SenS/SenR system for resistance against high concentrations of iron ions
and hemin in vivo. Hence SenS/SenR and HbpS act in concert as a novel three-component system which detects redox stress, mediated
by iron ions and heme. 相似文献