全文获取类型
收费全文 | 868篇 |
免费 | 144篇 |
国内免费 | 1篇 |
专业分类
1013篇 |
出版年
2022年 | 8篇 |
2021年 | 14篇 |
2020年 | 5篇 |
2019年 | 6篇 |
2018年 | 11篇 |
2017年 | 8篇 |
2016年 | 16篇 |
2015年 | 28篇 |
2014年 | 31篇 |
2013年 | 39篇 |
2012年 | 47篇 |
2011年 | 42篇 |
2010年 | 39篇 |
2009年 | 22篇 |
2008年 | 36篇 |
2007年 | 33篇 |
2006年 | 49篇 |
2005年 | 38篇 |
2004年 | 23篇 |
2003年 | 34篇 |
2002年 | 43篇 |
2001年 | 41篇 |
2000年 | 40篇 |
1999年 | 41篇 |
1998年 | 23篇 |
1997年 | 20篇 |
1996年 | 16篇 |
1995年 | 11篇 |
1994年 | 11篇 |
1993年 | 8篇 |
1992年 | 21篇 |
1991年 | 10篇 |
1990年 | 18篇 |
1989年 | 22篇 |
1988年 | 16篇 |
1987年 | 16篇 |
1986年 | 14篇 |
1985年 | 9篇 |
1984年 | 14篇 |
1983年 | 9篇 |
1982年 | 16篇 |
1981年 | 6篇 |
1980年 | 8篇 |
1979年 | 4篇 |
1978年 | 7篇 |
1977年 | 6篇 |
1976年 | 5篇 |
1975年 | 6篇 |
1974年 | 5篇 |
1966年 | 3篇 |
排序方式: 共有1013条查询结果,搜索用时 15 毫秒
51.
Zhang W Zitron E Hömme M Kihm L Morath C Scherer D Hegge S Thomas D Schmitt CP Zeier M Katus H Karle C Schwenger V 《The Journal of biological chemistry》2007,282(29):20933-20940
Aquaporin-1 (AQP1) channels contribute to osmotically induced water transport in several organs including the kidney and serosal membranes such as the peritoneum and the pleura. In addition, AQP1 channels have been shown to conduct cationic currents upon stimulation by cyclic nucleotides. To date, the short term regulation of AQP1 function by other major intracellular signaling pathways has not been studied. In the present study, we therefore investigated the regulation of AQP1 by protein kinase C. AQP1 wild type channels were expressed in Xenopus oocytes. Water permeability was assessed by hypotonic challenges. Activation of protein kinase C (PKC) by 1-oleoyl-2-acetyl-sn-glycerol (OAG) induced a marked increase of AQP1-dependent water permeability. This regulation was abolished in mutated AQP1 channels lacking both consensus PKC phosphorylation sites Thr(157) and Thr(239) (termed AQP1 DeltaPKC). AQP1 cationic currents measured with double-electrode voltage clamp were markedly increased after pharmacological activation of PKC by either OAG or phorbol 12-myristate 13-acetate. Deletion of either Thr(157) or Thr(239) caused a marked attenuation of PKC-dependent current increases, and deletion of both phosphorylation sites in AQP1 DeltaPKC channels abolished the effect. In vitro phosphorylation studies with synthesized peptides corresponding to amino acids 154-168 and 236-250 revealed that both Thr(157) and Thr(239) are phosphorylated by PKC. Upon stimulation by cyclic nucleotides, AQP1 wild type currents exhibited a strong activation. This regulation was not affected after deletion of PKC phosphorylation sites in AQP1 DeltaPKC channels. In conclusion, this is the first study to show that PKC positively regulates both water permeability and ionic conductance of AQP1 channels. This new pathway of AQP1 regulation is independent of the previously described cyclic nucleotide pathway and may contribute to the PKC stimulation of AQP1-modulated processes such as endothelial permeability, angiogenesis, and urine concentration. 相似文献
52.
53.
Combined monte carlo and molecular dynamics simulation of fully hydrated dioleyl and palmitoyl-oleyl phosphatidylcholine lipid bilayers 下载免费PDF全文
We have applied a new equilibration procedure for the atomic level simulation of a hydrated lipid bilayer to hydrated bilayers of dioleyl-phosphatidylcholine (DOPC) and palmitoyl-oleyl phosphatidylcholine (POPC). The procedure consists of alternating molecular dynamics trajectory calculations in a constant surface tension and temperature ensemble with configurational bias Monte Carlo moves to different regions of the configuration space of the bilayer in a constant volume and temperature ensemble. The procedure is applied to bilayers of 128 molecules of POPC with 4628 water molecules, and 128 molecules of DOPC with 4825 water molecules. Progress toward equilibration is almost three times as fast in central processing unit (CPU) time compared with a purely molecular dynamics (MD) simulation. Equilibration is complete, as judged by the lack of energy drift in 200-ps runs of continuous MD. After the equilibrium state was reached, as determined by agreement between the simulation volume per lipid molecule with experiment, continuous MD was run in an ensemble in which the lateral area was restrained to fluctuate about a mean value and a pressure of 1 atm applied normal to the bilayer surface. Three separate continuous MD runs, 200 ps in duration each, separated by 10,000 CBMC steps, were carried out for each system. Properties of the systems were calculated and averaged over the three separate runs. Results of the simulations are presented and compared with experimental data and with other recent simulations of POPC and DOPC. Analysis of the hydration environment in the headgroups supports a mechanism by which unsaturation contributes to reduced transition temperatures. In this view, the relatively horizontal orientation of the unsaturated bond increases the area per lipid, resulting in increased water penetration between the headgroups. As a result the headgroup-headgroup interactions are attenuated and shielded, and this contributes to the lowered transition temperature. 相似文献
54.
55.
Members of all four families of methanogenic bacteria were analyzed for polyamine concentrations. High-performance liquid chromatography analysis of dansylated cell extracts revealed typical polyamine patterns for each family. Members of Methanobacteriaceae (family I) were characterized by very low polyamine concentrations; members of Methanococcaceae (family II) were characterized by putrescine and high spermidine concentrations; members of Methanomicrobiaceae (family III) were characterized by the presence of putrescine, spermidine, and sym-homospermidine; and members of Methanosarcinaceae (family IV) contained only high concentrations of sym-homospermidine in addition to putrescine. The highest polyamine concentration was found in Methanosarcina barkeri Jülich, with 0.35% putrescine in the dry cell material. The polyamine distribution found coincides with the dendrogram based on comparative cataloguing of 16S rRNA and offers a new, rapid chemotaxonomic method for characterizing methanogenic bacteria. Variation of the growth substrates (H2-CO2, methanol, acetate, and trimethylamine) for M. barkeri resulted in quantitative but not qualitative differences in polyamine composition. 相似文献
56.
Fine mapping of the Autosomal Dominant Split Hand/Split Foot Locus on Chromosome 7, Band q21.3-q22.1 总被引:3,自引:3,他引:3 下载免费PDF全文
Stephen W. Scherer Parvoneh Poorkaj Todd Allen Julia Kim Dorrit Geshuri Mark Nunes Sylvia Soder Karen Stephens Roberta A. Pagon Michael A. Patton Mary Anne Berg Tim Donlon Horacio Rivera R. A. Pfeiffer Kenji Naritomi Helen Hughes Maurizio Genuardi Fiorella Gurrieri Giovanni Neri Everett Lovrein Ellen Magenis Lap-Chee Tsui James P. Evans 《American journal of human genetics》1994,55(1):12-20
Split hand/split foot (SHFD) is a human developmental defect characterized by missing digits, fusion of remaining digits, and a deep median cleft in the hands and feet. Cytogenetic studies of deletions and translocations associated with this disorder have indicated that an autosomal dominant split hand/split foot locus (gene SHFD1) maps to 7q21-q22. To characterize the SHFD1 locus, somatic cell hybrid lines were constructed from cytogenetically abnormal individuals with SHFD. Molecular analysis resulted in the localization of 93 DNA markers to one of 10 intervals surrounding the SHFD1 locus. The translocation breakpoints in four SHFD patients were encompassed by the smallest region of overlap among the SHFD-associated deletions. The order of DNA markers in the SHFD1 critical region has been defined as PON–D7S812–SHFD1–D7S811–ASNS. One DNA marker, D7S811, detected altered restriction enzyme fragments in three patients with translocations when examined by pulsed-field gel electro-phoresis (PFGE). These data map SHFD1, a gene that is crucial for human limb differentiation, to a small interval in the q21.3-q22.1 region of human chromosome 7. 相似文献
57.
Nucleotide sequence of the O gene and of the origin of replication in bacteriophage lambda DNA. 总被引:11,自引:11,他引:11 下载免费PDF全文
G Scherer 《Nucleic acids research》1978,5(9):3141-3156
The nucleotide sequence of the O gene in bacteriophage lambda DNA is presented. According to two possible initiator codons, the primary structure of the O protein deduced from the DNA sequence consists of 278 or 299 amino acid residues. Structure and function of the O protein--one of the two phage initiator proteins for lambda DNA replication--are discussed in the light of a secondary structure model for the O protein. The central part of the O gene contains a cluster of symmetrical sequences extending over 160 base pairs. The point mutation of the cis-dominant replication mutant ti12 is located in this region. 相似文献
58.
In vitro stimulation by 2,4-dichlorophenoxyacetic acid of an ATPase and inhibition of phosphatidate phosphatase of plant membranes. 总被引:1,自引:0,他引:1
The auxin herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) was shown to modulate the activities of several phosphatases with membranes isolated from soybean hypocotyls under conditions where degradative changes in the membranes were minimized. The medium for isolation of membranes consisted of 0.1 M Tris/HCl or Tris/acetate, pH 6.5, 0.5 M sucrose, 4% choline () and 4% ethanolamine () to inhibit phospholipase D, 20 mM EGTA [ethyleneglycol-bis- (β aminoethyl ether) N,N-tetracetic acid] and 1 mM nupercaine, to inhibit phospholipase A. In contrast, the inactive auxin analog 2,3-D, did not influence ATPase activity. Endogenous release of inorganic phosphate from an unidentified source was also stimulated 30% by 2,4-D. Phosphatidate phosphatase was inhibited by 2,4-D, whereas hydrolysis of glucose-6-phosphate was not influenced by 2,4-D under the same conditions. These observations may be of relevance to the proton pump hypothesis of growth regulation. 相似文献
59.
The optical spectra of the reaction center (RC) of Rhodopseudomonas viridis including absorption (A), linear dichrosism (LD), circular dichroism (CD), absorption-detected magnetic resonance (ADMR) and its linear dichroism (LD-ADMR) are simulated by an exciton model. It involves the Qy transitions of six prosthetic groups: four (bacteriochlorophyll-b molecules, two bacteriopheophytin-b molecules and the Soret bands By of the special-pair pigments, which couple most strongly with the corresponding Qy transitions. For the ADMR-spectra additional excitations of the special-pair triplet are introduced. While interactions between the Qy transitions and the By transitions are in principle determined from the structural arrangement of the pigments, the interactions to the other states are adjusted to fit the spectral features for the various transitions. The interaction of the newly introduced states are interpreted in terms of a simple model. 相似文献
60.
T Scherer C Lindtner E Zielinski J O'Hare N Filatova C Buettner 《The Journal of biological chemistry》2012,287(39):33061-33069
Insulin controls fatty acid (FA) release from white adipose tissue (WAT) through direct effects on adipocytes and indirectly through hypothalamic signaling by reducing sympathetic nervous system outflow to WAT. Uncontrolled FA release from WAT promotes lipotoxicity, which is characterized by inflammation and insulin resistance that leads to and worsens type 2 diabetes. Here we tested whether early diet-induced insulin resistance impairs the ability of hypothalamic insulin to regulate WAT lipolysis and thus contributes to adipose tissue dysfunction. To this end we fed male Sprague-Dawley rats a 10% lard diet (high fat diet (HFD)) for 3 consecutive days, which is known to induce systemic insulin resistance. Rats were studied by euglycemic pancreatic clamps and concomitant infusion of either insulin or vehicle into the mediobasal hypothalamus. Short term HFD feeding led to a 37% increase in caloric intake and elevated base-line free FAs and insulin levels compared with rats fed regular chow. Overfeeding did not impair insulin signaling in WAT, but it abolished the ability of mediobasal hypothalamus insulin to suppress WAT lipolysis and hepatic glucose production as assessed by glycerol and glucose flux. HFD feeding also increased hypothalamic levels of the endocannabinoid 2-arachidonoylglycerol after only 3 days. In summary, overfeeding impairs hypothalamic insulin action, which may contribute to unrestrained lipolysis seen in human obesity and type 2 diabetes. 相似文献