全文获取类型
收费全文 | 292篇 |
免费 | 25篇 |
专业分类
317篇 |
出版年
2023年 | 4篇 |
2022年 | 4篇 |
2021年 | 6篇 |
2020年 | 5篇 |
2019年 | 5篇 |
2018年 | 11篇 |
2017年 | 7篇 |
2016年 | 7篇 |
2015年 | 12篇 |
2014年 | 11篇 |
2013年 | 17篇 |
2012年 | 21篇 |
2011年 | 22篇 |
2010年 | 17篇 |
2009年 | 11篇 |
2008年 | 11篇 |
2007年 | 10篇 |
2006年 | 13篇 |
2005年 | 22篇 |
2004年 | 14篇 |
2003年 | 11篇 |
2002年 | 10篇 |
2001年 | 4篇 |
2000年 | 4篇 |
1999年 | 12篇 |
1998年 | 2篇 |
1997年 | 4篇 |
1996年 | 5篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1980年 | 1篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 2篇 |
1968年 | 3篇 |
1964年 | 1篇 |
排序方式: 共有317条查询结果,搜索用时 0 毫秒
31.
To understand the mechanism of kinesin movement we have investigated the relative configuration of the two kinesin motor domains during ATP hydrolysis using fluorescence polarization microscopy of ensemble and single molecules. We found that: (i) in nucleotide states that induce strong microtubule binding, both motor domains are bound to the microtubule with similar orientations; (ii) this orientation is maintained during processive motion in the presence of ATP; (iii) the neck-linker region of the motor domain has distinct configurations for each nucleotide condition tested. Our results fit well with a hand-over-hand type movement mechanism and suggest how the ATPase cycle in the two motor domains is coordinated. We propose that the motor neck-linker domain configuration controls ADP release. 相似文献
32.
Puentes A García J Ocampo M Rodríguez L Vera R Curtidor H López R Suarez J Valbuena J Vanegas M Guzman F Tovar D Patarroyo ME 《Peptides》2003,24(7):1015-1023
This work determined Plasmodium falciparum merozoite surface protein-8 (MSP-8) regions specifically binding to membrane surface receptors on human erythrocytes. Five high activity binding peptides (HABPs), whose binding to erythrocytes became saturable and sensitive on being treated with neuraminidase and chymotrypsin were identified from the MSP-8 protein. Those amino acids directly involved in interaction with erythrocytes were also determined for each one of the HABPs. Some of them specifically recognized 28, 46, and 73 kDa erythrocyte membrane proteins. Some HABPs inhibited in vitro P. falciparum merozoite invasion of erythrocytes by up to 98%, suggesting the MSP-8 protein's possible role in the invasion process. 相似文献
33.
Grandoso G Avila P Cayón A Hernando MA Llosa M de la Cruz F 《Journal of molecular biology》2000,295(5):1163-1172
Protein TrwC is the relaxase-helicase responsible for the initiation and termination reactions of DNA processing during plasmid R388 conjugation. Site-directed mutagenesis was used to change to phenylalanine each of a set of four conserved tyrosyl residues in the sequence of the N-terminal relaxation domain of the protein. Simultaneous mutation of both Y18 and Y26 was required to abolish in vitro cleavage and strand-transfer reactions catalyzed by protein TrwC on oligonucleotides containing the nic site. Thus, both Y18 and Y26 could be involved independently in the formation of oligonucleotide-protein covalent complexes that constitute presumed intermediates of these reactions. This hypothesis was confirmed by the observation of Y18 and Y26-specific peptide-oligonucleotide adducts after protease digestion of TrwC and mutant derivatives. Finally mutation Y18F, but not mutation Y26F, abolished nic-cleavage of a supercoiled DNA containing the R388 origin of transfer (oriT). These data allowed the construction of a model for conjugative DNA processing in which Y18 specifically catalyzes the initial cleavage reaction, while Y26 is used for the second strand-transfer reaction, which terminates conjugation. The model suggests a control mechanism that can be effective at each conjugative replication cycle. 相似文献
34.
de la Horra C Hernando N Lambert G Forster I Biber J Murer H 《The Journal of biological chemistry》2000,275(9):6284-6287
Type II Na/P(i) cotransporters play key roles in epithelial P(i) transport and thereby contribute to overall P(i) homeostasis. Renal proximal tubular brush border membrane expresses the IIa isoform, whereas the IIb isoform is preferentially expressed in small intestinal brush border membrane of mammals. IIa and IIb proteins are predicted to contain eight transmembrane domains with the N- and C-terminal tails facing the cytoplasm. They differ in their pH dependences: the activity of IIa increases at higher pH, whereas the IIb shows no or a slightly opposite pH dependence. To determine the structural domains responsible for the difference in pH sensitivity, mouse IIa and IIb chimeras were constructed, and their pH dependence was characterized. A region between the fourth and fifth transmembrane domains was required for conferring pH sensitivity to the IIa-mediated Na/P(i) cotransport. Sequence comparison (IIa versus IIb) of the third extracellular loops revealed a stretch of three charged amino acids in IIa (REK) replaced by uncharged residues in IIb (GNT). Introduction of the uncharged GNT sequence (by REK) in IIa abolished its pH dependence, whereas introduction of the charged REK stretch in IIb (by GNT) led to a pH dependence similar to IIa. These findings suggest that charged residues within the third extracellular loop are involved in the pH sensitivity of IIa Na/P(i) cotransporter. 相似文献
35.
M. Rosa Bernal-López Ainhoa Rípodas Paloma Aragoncillo Manuel Gil Aguado Francisco Javier Serrano Hernando Francisco J. Tinahones Ricardo Gómez-Huelgas Arturo Fernández-Cruz 《Process Biochemistry》2009,44(11):1231-1236
Endothelin-1 (ET-1) is a potent vasoconstrictor peptide that can modulate the behaviour of vascular smooth muscle cells and thus impact on the development of human atherosclerosis. Circulating plasma levels of ET-1 were measured from 82 patients with ischemic cardiomyopathy (ICM) and 42 healthy controls. A significant increase was found in plasma levels of ET-1 in the patients compared to the controls. These circulating levels of ET-1 were greater in patients with diabetes or involvement of several territories. Gene expression of pre-proET-1 and its receptors ETA and ETB was analyzed in the atheromatous plaques from carotid arteries (n = 8) and the internal mammary artery (IMA) (n = 8). Our group observed an increase in pre-proET-1 and ETA in IMA compared with the atheromatous plaques. Immunohistochemical studies in the atherosclerotic plaque showed that the expression of ET-1 was greater in the areas where the macrophages and lipid nucleus were located.Our findings in this group of patients with symptomatic vascular disease suggest that the endothelin system may play an important role in atherothrombosis. 相似文献
36.
37.
César Garriga Patricia García de Olalla Josep M. Miró Inma Oca?a Hernando Knobel Maria Jesús Barberá Victoria Humet Pere Domingo Josep M. Gatell Esteve Ribera Mercè Gurguí Andrés Marco Joan A. Caylà 《PloS one》2015,10(12)
Introduction
Antiretroviral therapy has led to a decrease in HIV-related mortality and to the emergence of non-AIDS defining diseases as competing causes of death. This study estimates the HIV mortality rate and their risk factors with regard to different causes in a large city from January 2001 to June 2013.Materials and Methods
We followed-up 3137 newly diagnosed HIV non-AIDS cases. Causes of death were classified as HIV-related, non-HIV-related and external. We examined the effect of risk factors on survival using mortality rates, Kaplan-Meier plots and Cox models. Finally, we estimated survival for each main cause of death groups through Fine and Gray models.Mortality Results
182 deaths were found [14.0/1000 person-years of follow-up (py); 95% confidence interval (CI):12.0–16.1/1000 py], 81.3% of them had a known cause of death. Mortality rate by HIV-related causes and non-HIV-related causes was the same (4.9/1000 py; CI:3.7–6.1/1000 py), external was lower [1.7/1000 py; (1.0–2.4/1000 py)].Survival Results
Kaplan-Meier estimate showed worse survival in intravenous drug user (IDU) and heterosexuals than in men having sex with men (MSM). Factors associated with HIV-related causes of death include: IDU male (subHazard Ratio (sHR):3.2; CI:1.5–7.0) and <200 CD4 at diagnosis (sHR:2.7; CI:1.3–5.7) versus ≥500 CD4. Factors associated with non-HIV-related causes of death include: ageing (sHR:1.5; CI:1.4–1.7) and heterosexual female (sHR:2.8; CI:1.1–7.3) versus MSM. Factors associated with external causes of death were IDU male (sHR:28.7; CI:6.7–123.2) and heterosexual male (sHR:11.8; CI:2.5–56.4) versus MSM.Conclusion and Recommendation
There are important differences in survival among transmission groups. Improved treatment is especially necessary in IDUs and heterosexual males. 相似文献38.
39.
40.
Genetic diversity, structure, and size of an endangered brown bear population threatened by highway construction in the Pindos Mountains, Greece 总被引:1,自引:0,他引:1
Alexandros A. Karamanlidis Martin Straka Elena Drosopoulou Miguel de Gabriel Hernando Ivna Kocijan Ladislav Paule Zacharias Scouras 《European Journal of Wildlife Research》2012,58(3):511-522
One of the major negative effects of roads is the creation of barriers to the movement of wildlife, ultimately disconnecting populations and increasing extinction risk. We collected genetic data from a threatened brown bear population in the central part of the Pindos mountain range in northwestern Greece to provide information about this, as yet genetically undescribed, population and to evaluate its status prior to the construction of a major highway. We used noninvasive genetic sampling methods and microsatellite analysis to investigate nuclear genetic diversity, population genetic structure, demographic history, relatedness within the population and estimated effective and total population size. Brown bears in the study area were found to possess a relatively high level of nuclear genetic diversity and low levels of inbreeding; the population did not show any signs of substructuring but seems to have gone through a genetic bottleneck in the recent past. The estimated effective population size was 29, and the total population size estimate obtained by two different methods was 33 and 51 individuals, respectively. Our results indicate a good conservation status of this bear population and provide baseline genetic data for the future evaluation of the effects on bears from the construction of a major highway, for monitoring the genetic status of this and other bear populations in Greece and for assessing gene flow in bear populations in southern Europe. 相似文献