全文获取类型
收费全文 | 619篇 |
免费 | 59篇 |
出版年
2023年 | 4篇 |
2021年 | 6篇 |
2020年 | 4篇 |
2018年 | 7篇 |
2017年 | 7篇 |
2016年 | 12篇 |
2015年 | 11篇 |
2014年 | 26篇 |
2013年 | 22篇 |
2012年 | 32篇 |
2011年 | 29篇 |
2010年 | 22篇 |
2009年 | 16篇 |
2008年 | 22篇 |
2007年 | 25篇 |
2006年 | 23篇 |
2005年 | 20篇 |
2004年 | 20篇 |
2003年 | 25篇 |
2002年 | 30篇 |
2001年 | 25篇 |
2000年 | 15篇 |
1999年 | 18篇 |
1998年 | 10篇 |
1997年 | 9篇 |
1995年 | 8篇 |
1994年 | 7篇 |
1993年 | 9篇 |
1992年 | 16篇 |
1991年 | 12篇 |
1990年 | 19篇 |
1989年 | 14篇 |
1988年 | 7篇 |
1987年 | 15篇 |
1986年 | 8篇 |
1985年 | 13篇 |
1984年 | 7篇 |
1983年 | 10篇 |
1982年 | 6篇 |
1981年 | 6篇 |
1980年 | 8篇 |
1979年 | 6篇 |
1978年 | 4篇 |
1977年 | 5篇 |
1975年 | 6篇 |
1974年 | 6篇 |
1973年 | 6篇 |
1971年 | 3篇 |
1970年 | 4篇 |
1968年 | 3篇 |
排序方式: 共有678条查询结果,搜索用时 112 毫秒
51.
Ahn K Yeyeodu S Collette J Madden V Arthur J Li L Erickson AH 《Traffic (Copenhagen, Denmark)》2002,3(2):147-159
In transformed mouse fibroblasts, a significant proportion of the lysosomal cysteine protease cathepsin L remains in cells as an inactive precursor which associates with membranes by a mannose phosphate-independent interaction. When microsomes prepared from these cells were resolved on sucrose gradients, this procathepsin L was localized in dense vesicles distinct from those enriched for growth hormone, which is secreted constitutively when expressed in fibroblasts. Ultrastructural studies using antibodies directed against the propeptide to avoid detection of the mature enzyme in lysosomes revealed that the proenzyme was concentrated in dense cores within small vesicles and multivesicular endosomes which labeled with antibodies specific for CD63. Consistent with the resemblance of these cores to those of regulated secretory granules, secretion of procathepsin L from fibroblasts was modestly stimulated by phorbol, 12-myristate, 13-acetate. When protein synthesis was blocked with cycloheximide and lysosomal proteolysis inhibited with leupeptin, procathepsin L was found to gradually convert to the active single-chain protease. The data suggest that when synthesis levels are high, a portion of the procathepsin L is packaged in dense cores within multivesicular endosomes localized near the plasma membrane. Gradual activation of this proenzyme achieves targeting of the proenzyme to lysosomes by a mannose phosphate receptor-independent pathway. 相似文献
52.
The saliva of ticks contains a complex mixture of bioactive molecules including proteins that modulate host responses ensuring
successful feeding. The limited amount of saliva that can be obtained from ticks has hampered characterization of salivary
proteins using traditional protein chemistry. Recent improvements in two-dimensional gel electrophoresis, mass spectrometry,
and bioinformatics provide new tools to characterize small amounts of protein. These methods were employed to characterize
salivary proteins from Amblyomma americanum and Amblyomma maculatum. Salivation was induced by injection of dopamine and theophylline. It was necessary to desalt and concentrate saliva before
analysis by 2-D electrophoresis. Comparison of 1-D and 2-D gel patterns revealed that the major protein component of saliva
did not appear on 2-D gels. Characterization of this protein showed that it was identical to the major protein present in
the hemolymph of both tick species. Protein profiles obtained by 1-D and 2-D gel electrophoresis were similar for both tick
species, however, higher concentrations of lower molecular weight proteins were present in A. maculatum. Protein analysis by MALDI-TOF mass spectrometry and western blot analysis showed that except for the most abundant protein
with a molecular weight of 95 kDa, all of the proteins detected were of host origin. It is not known if this is an artifact
of the collection method or has physiological significance. In either case, in these species of ticks, host proteins will
have to be removed from saliva samples prior to 2-D analysis in order to characterize lower abundance proteins of tick origin.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
53.
Madden SF O'Donovan B Furney SJ Brady HR Silvestre G Doran PP 《Bioinformatics (Oxford, England)》2003,19(12):1594-1595
Digital Extractor is a program for the high-throughput processing of data sets derived from digital differential display-based comparisons of EST libraries. These comparisons can be utilized to identify discrete subsets of genes whose expression is restricted to distinct tissue types. The program facilitates these investigations by permitting parallel annotation of genes identified as being differentially expressed. 相似文献
54.
1. The rostral ventrolateral medulla (RVLM) is essential for the normal control of arterial pressure. This region of the brainstem is heterogeneous, and contains spinally projecting neurons that contain phenylethanolamine-N-methyltransferase (C1 neurons) and non-C1 neurons.2. The availability of a toxin, a dopamine--hydroxylase antibody conjugated to saporin, that can selectively destroy C1 neurons within the RVLM allows for the study of cardiovascular regulation in rats following depletion of the C1 neuronal population.3. C1 neurons are not essential for the maintenance of resting blood pressure in anesthetized rats, but do contribute to many cardiovascular responses mediated through the RVLM.4. The depressor response elicited by clonidine injected into the RVLM is dependent upon C1 neurons.5. Studies in rats with selective toxin-induced destruction of RVLM C1 neurons demonstrate that C1 neurons contribute importantly to cardiovascular regulation. 相似文献
55.
Wheeler DL Church DM Lash AE Leipe DD Madden TL Pontius JU Schuler GD Schriml LM Tatusova TA Wagner L Rapp BA 《Nucleic acids research》2001,29(1):11-16
In addition to maintaining the GenBank nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides data analysis and retrieval resources that operate on the data in GenBank and a variety of other biological data made available through NCBI's Web site. NCBI data retrieval resources include Entrez, PubMed, LocusLink and the Taxonomy Browser. Data analysis resources include BLAST, Electronic PCR, OrfFinder, RefSeq, UniGene, HomoloGene, Database of Single Nucleotide Polymorphisms (dbSNP), Human Genome Sequencing, Human MapViewer, GeneMap'99, Human-Mouse Homology Map, Cancer Chromosome Aberration Project (CCAP), Entrez Genomes, Clusters of Orthologous Groups (COGs) database, Retroviral Genotyping Tools, Cancer Genome Anatomy Project (CGAP), SAGEmap, Gene Expression Omnibus (GEO), Online Mendelian Inheri-tance in Man (OMIM), the Molecular Modeling Database (MMDB) and the Conserved Domain Database (CDD). Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of the resources can be accessed through the NCBI home page at: http://www.ncbi.nlm.nih. gov. 相似文献
56.
Halla TR Madden JA Gordon JB 《American journal of physiology. Lung cellular and molecular physiology》2000,278(5):L968-L973
Pulmonary venous constriction leads to significant pulmonary hypertension and increased edema formation in several models using newborns. Although alkalosis is widely used in treating neonatal and pediatric pulmonary hypertension, its effects on pulmonary venous tone have not previously been directly measured. This study sought to determine whether alkalosis caused pulmonary venous relaxation and, if so, to identify the mediator(s) involved. Pulmonary venous rings (500-microm external diameter) were isolated from 1-wk-old piglets and precontracted with the thromboxane mimetic U-46619. Responses to hypocapnic alkalosis were then measured under control conditions after inhibition of endothelium-derived modulator activity or K(+) channels. In control rings, alkalosis caused a 34.4 +/- 4.8% decrease in the U-46619-induced contraction. This relaxation was significantly blunted in rings without functional endothelium and in rings treated with nitric oxide synthase or guanylate cyclase inhibitors. However, neither cyclooxygenase inhibition nor voltage-dependent, calcium-dependent, or ATP-dependent K(+)-channel inhibitors altered alkalosis-induced relaxation. These data suggest that alkalosis caused significant dilation of piglet pulmonary veins that was mediated by the nitric oxide-cGMP pathway. 相似文献
57.
Short-lived free radicals formed in the reaction of 11 substrates and radiolytically produced hydroxyl radicals were trapped successfully with 5, 5-dimethyl-1-pyrroline-N-oxide (DMPO) in dilute aqueous solution. The in situ radiolysis steady-state ESR spectra of the spin adducts were analyzed to determine accurate ESR parameters for these spin adducts in a uniform environment. Parent alkyl radicals include methyl, ethyl, 1-propyl and 2-propyl (1-methylethyl). Hydroxyalkyl parent radicals were hydroxymethyl, hydroxyethyl, 2-hydroxy-2-propyl (1-methyl-1-hydroxyethyl), 1-hydroxypropyl and 2-hydroxy-2-methylpropyl. Carboxyl radical (carbon dioxide anion, formate radical) and sulfite anion radical were the sigma radicals studied. The DMPO spin adduct of 1-propyl was identified for the first time. For most spin adducts, g factors were also determined for the first time. In DMPO spin adducts of hydroxyalkyl radicals, nitrogen and C(2)-proton hyperfine coupling constants are smaller than those of alkyl radical adducts; the hydroxyalkyl spin adducts possess larger g values than their unsubstituted counterparts. These changes are ascribed to the spread of pi conjugation to include the hydroxyl group. Strong evidence of spin addend-aminoxyl group interaction can be seen in the asymmetrical line shapes in the hydroxyethyl and the hydroxypropyl spin adducts. 相似文献
58.
van Dijken JP Bauer J Brambilla L Duboc P Francois JM Gancedo C Giuseppin ML Heijnen JJ Hoare M Lange HC Madden EA Niederberger P Nielsen J Parrou JL Petit T Porro D Reuss M van Riel N Rizzi M Steensma HY Verrips CT Vindeløv J Pronk JT 《Enzyme and microbial technology》2000,26(9-10):706-714
To select a Saccharomyces cerevisiae reference strain amenable to experimental techniques used in (molecular) genetic, physiological and biochemical engineering research, a variety of properties were studied in four diploid, prototrophic laboratory strains. The following parameters were investigated: 1) maximum specific growth rate in shake-flask cultures; 2) biomass yields on glucose during growth on defined media in batch cultures and steady-state chemostat cultures under controlled conditions with respect to pH and dissolved oxygen concentration; 3) the critical specific growth rate above which aerobic fermentation becomes apparent in glucose-limited accelerostat cultures; 4) sporulation and mating efficiency; and 5) transformation efficiency via the lithium-acetate, bicine, and electroporation methods. On the basis of physiological as well as genetic properties, strains from the CEN.PK family were selected as a platform for cell-factory research on the stoichiometry and kinetics of growth and product formation. 相似文献
59.
Out of Africa and back again: nested cladistic analysis of human Y chromosome variation 总被引:18,自引:3,他引:15
Hammer MF; Karafet T; Rasanayagam A; Wood ET; Altheide TK; Jenkins T; Griffiths RC; Templeton AR; Zegura SL 《Molecular biology and evolution》1998,15(4):427-441
We surveyed nine diallelic polymorphic sites on the Y chromosomes of 1,544
individuals from Africa, Asia, Europe, Oceania, and the New World.
Phylogenetic analyses of these nine sites resulted in a tree for 10
distinct Y haplotypes with a coalescence time of approximately 150,000
years. The 10 haplotypes were unevenly distributed among human populations:
5 were restricted to a particular continent, 2 were shared between Africa
and Europe, 1 was present only in the Old World, and 2 were found in all
geographic regions surveyed. The ancestral haplotype was limited to African
populations. Random permutation procedures revealed statistically
significant patterns of geographical structuring of this paternal genetic
variation. The results of a nested cladistic analysis indicated that these
geographical associations arose through a combination of processes,
including restricted, recurrent gene flow (isolation by distance) and range
expansions. We inferred that one of the oldest events in the nested
cladistic analysis was a range expansion out of Africa which resulted in
the complete replacement of Y chromosomes throughout the Old World, a
finding consistent with many versions of the Out of Africa Replacement
Model. A second and more recent range expansion brought Asian Y chromosomes
back to Africa without replacing the indigenous African male gene pool.
Thus, the previously observed high levels of Y chromosomal genetic
diversity in Africa may be due in part to bidirectional population
movements. Finally, a comparison of our results with those from nested
cladistic analyses of human mtDNA and beta-globin data revealed different
patterns of inferences for males and females concerning the relative roles
of population history (range expansions) and population structure
(recurrent gene flow), thereby adding a new sex-specific component to
models of human evolution.
相似文献