全文获取类型
收费全文 | 357篇 |
免费 | 43篇 |
出版年
2018年 | 4篇 |
2017年 | 4篇 |
2016年 | 3篇 |
2015年 | 6篇 |
2014年 | 4篇 |
2013年 | 16篇 |
2012年 | 7篇 |
2011年 | 17篇 |
2010年 | 9篇 |
2009年 | 9篇 |
2008年 | 14篇 |
2007年 | 8篇 |
2006年 | 17篇 |
2005年 | 10篇 |
2004年 | 15篇 |
2003年 | 10篇 |
2002年 | 7篇 |
2001年 | 14篇 |
2000年 | 8篇 |
1999年 | 4篇 |
1998年 | 8篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1995年 | 5篇 |
1994年 | 3篇 |
1992年 | 7篇 |
1991年 | 9篇 |
1990年 | 6篇 |
1989年 | 13篇 |
1988年 | 9篇 |
1987年 | 10篇 |
1986年 | 4篇 |
1985年 | 6篇 |
1984年 | 9篇 |
1983年 | 10篇 |
1982年 | 5篇 |
1981年 | 7篇 |
1980年 | 7篇 |
1979年 | 7篇 |
1978年 | 6篇 |
1977年 | 7篇 |
1976年 | 8篇 |
1974年 | 4篇 |
1973年 | 6篇 |
1972年 | 4篇 |
1969年 | 4篇 |
1968年 | 5篇 |
1967年 | 4篇 |
1951年 | 2篇 |
1919年 | 4篇 |
排序方式: 共有400条查询结果,搜索用时 15 毫秒
101.
Sentinel lymph nodes (SLNs), being the first nodes to receive lymph from a primary tumour and the preferential site of initial tumour metastases, are intensively exposed to the bioactive products of tumour cells and other associated cells. This makes them ideal for studies of the factors that determine selective tissue susceptibility to metastases. We postulate that tumour-induced immune modulation of SLNs facilitates lymph-node metastases by inhibiting the generation of tumour-specific cytotoxic T cells that are active against tumour cells of primary and metastatic melanomas. Immune modulation of the lymph nodes can be reversed by granulocyte/macrophage colony-stimulating factor (GM-CSF), a finding that has implications for the future therapy of lymph-node metastases. 相似文献
102.
Cochran DA Evans CA Blinco D Burthem J Stevenson FK Gaskell SJ Whetton AD 《Molecular & cellular proteomics : MCP》2003,2(12):1331-1341
Chronic lymphocytic leukemia (CLL) is a common hematopoietic malignant disease with variable outcome. CLL has been divided into distinct groups based on whether somatic hypermutation has occurred in the variable region of the immunoglobulin heavy-chain locus or alternatively if the cells express higher levels of the CD38 protein. We have analyzed the proteome of 12 cases of CLL (six mutated (M-CLL) and six unmutated (UM-CLL) immunoglobulin heavy-chain loci; seven CD38-negative and five CD38-positive) using two-dimensional electrophoresis and mass spectrometry. Statistical evaluation using principal component analysis indicated significant differences in patterns of protein expression between the cases with and without somatic mutation. Specific proteins indicated by principal component analysis as varying between the prognostic groups were characterized using mass spectrometry. The levels of F-actin-capping protein beta subunit, 14-3-3 beta protein, and laminin-binding protein precursor were significantly increased in M-CLL relative to UM-CLL. In addition, primary sequence data from tandem mass spectrometry showed that nucleophosmin was present as several protein spots in M-CLL but was not detected in UM-CLL samples, suggesting that several post-translationally modified forms of nucleophosmin vary between these two sample groups. No specific differences were found between CD38-positive and -negative patient samples using the same approach. The results presented show that proteomic analysis can complement other approaches in identifying proteins that may have potential value in the biological and diagnostic distinction between important clinical subtypes of CLL. 相似文献
103.
104.
The genomes of homeothermic (warm-blooded) vertebrates are mosaic
interspersions of homogeneously GC-rich and GC-poor regions (isochores).
Evolution of genome compartmentalization and GC-rich isochores is
hypothesized to reflect either selective advantages of an elevated GC
content or chromosome location and mutational pressure associated with the
timing of DNA replication in germ cells. To address the present controversy
regarding the origins and maintenance of isochores in homeothermic
vertebrates, newly obtained as well as published nucleotide sequences of
the insulin and insulin-like growth factor (IGF) genes, members of a
well-characterized gene family believed to have evolved by repeated
duplication and divergence, were utilized to examine the evolution of base
composition in nonconstrained (flanking) and weakly constrained (introns
and fourfold degenerate sites) regions. A phylogeny derived from amino acid
sequences supports a common evolutionary history for the insulin/IGF family
genes. In cold- blooded vertebrates, insulin and the IGFs were similar in
base composition. In contrast, insulin and IGF-II demonstrate dramatic
increases in GC richness in mammals, but no such trend occurred in IGF- I.
Base composition of the coding portions of the insulin and IGF genes across
vertebrates correlated (r = 0.90) with that of the introns and flanking
regions. The GC content of homologous introns differed dramatically between
insulin/IGF-II and IGF-I genes in mammals but was similar to the GC level
of noncoding regions in neighboring genes. Our findings suggest that the
base composition of introns and flanking regions is determined by
chromosomal location and the mutational pressure of the isochore in which
the sequences are embedded. An elevated GC content at codon third positions
in the insulin and the IGF genes may reflect selective constraints on the
usage of synonymous codons.
相似文献
105.
Conversion of labelled 5 alpha-androstane-17 beta-ol-3-one (DHT) by isolated testicular cells from rats of different ages was examined under saturating substrate conditions in vitro (5--10 micrograms DHT/ml in a 24 h incubation). Two detectable metabolites of DHT were produced by testicular cells in vitro. 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol) and 5 alpha-androstane-3 beta, 17 beta-diol (3 beta-diol). Production of these diols during a 24 h period was linear, and the amounts formed were directly related to the cell number. The amount of 3 alpha- and 3 beta-diols formed by testicular cells of rats of different ages increased from Day 10 to Day 25, then declined. Testicular cells from rats 10 to 20 days of age converted DHT mainly to 3 alpha-diol, but thereafter 3 beta-diol was the predominant testicular metabolite of DHT. 相似文献
106.
The emission (from wastewater treatment plants) of airborne coliphages that form plaques on two strains of Escherichia coli was investigated. Two activated-sludge and two trickling-filter plants were studied. Field sampling procedures used large-volume air samplers with recirculation devices. Coliphages were enumerated by a most-probable-number (MPN) procedure. Temperature, relative humidity, windspeed, and presence of sunlight were monitored. Concurrent samples of sewage were taken during each air-sampling run. Average coliphage levels in the airborne emissions of trickling-filter beds and activated-sludge units were 2.84 X 10(-1) and 3.02 X 10(-1) MPN/m3, respectively, for all positive observations, and sewage liquor concentrations from the sources were 4.48 X 10(5) and 2.94 X 10(6) plaque-forming units/liter, respectively, depending upon the E. coli host used for assay. This work establishes minimal airborne-coliphage concentrations from the plants studied. The procedures employed will be useful in evaluating the animal virus levels in these emissions. 相似文献
107.
Donald G. Cochran 《Chromosoma》1976,59(2):129-135
Adjacent-1, alternate-1, adjacent-2, and alternate-2 disjunction configurations were observed cytologically at metaphase I in heterozygotes from two reciprocal chromosome translocations in the German cockroach, Blattella germanica (L.). T(7; 12) shows random disjunction and the frequencies of the above four types were in a ratio of 2112 (p>0.90). T(3; 12) has directed disjunction (about 70% alternate) which is attributable to a heavy preponderance of alternate-2. No interpretable ratio occurs here except for the equality of alternate-1 and adjacent-2 types. These observations confirm the existence of two types of alternate disjunction, and provide insight into the basis for random vs directed disjunction. 相似文献
108.
Skiniotis G Cochran JC Müller J Mandelkow E Gilbert SP Hoenger A 《The EMBO journal》2004,23(5):989-999
The flexible tubulin C-terminal tails (CTTs) have recently been implicated in the walking mechanism of dynein and kinesin. To address their role in the case of conventional kinesin, we examined the structure of kinesin-microtubule (MT) complexes before and after CTT cleavage by subtilisin. Our results show that the CTTs directly modulate the motor-tubulin interface and the binding properties of motors. CTT cleavage increases motor binding stability, and kinesin appears to adopt a binding conformation close to the nucleotide-free configuration under most nucleotide conditions. Moreover, C-terminal cleavage results in trapping a transient motor-ADP-MT intermediate. Using SH3-tagged dimeric and monomeric constructs, we could also show that the position of the kinesin neck is not affected by the C-terminal segments of tubulin. Overall, our study reveals that the tubulin C-termini define the stability of the MT-kinesin complex in a nucleotide-dependent manner, and highlights the involvement of tubulin in the regulation of weak and strong kinesin binding states. 相似文献
109.
Fine epitope mapping of anti-epidermal growth factor receptor antibodies through random mutagenesis and yeast surface display 总被引:8,自引:0,他引:8
Fine epitope mapping of therapeutically relevant monoclonal antibodies (mAbs) specific for the epidermal growth factor receptor (EGFR) was accomplished through random mutagenesis and yeast surface display. Using this method, we have identified key residues energetically important for the binding of EGFR to the mAbs 806, 225, and 13A9. A yeast-displayed library of single point mutants of an EGFR ectodomain fragment (residues 273-621) was constructed by random mutagenesis and was screened for reduced binding to EGFR mAbs. If an EGFR mutant showed loss of binding to a mAb, this suggested that the mutated residue was potentially a contact residue. The mAb 806 binding epitope was localized to one face of a loop comprised of EGFR residues Cys287-Cys302, which is constrained by a disulfide bond and two salt bridges. The mAb 806 epitope as identified here is not fully accessible in the autoinhibited EGFR monomer conformation, which is consistent with the hypothesis that mAb 806 binds to a transitional form of EGFR as it changes from an autoinhibited to extended monomer. The amino acids Lys465 and Ile467 were identified as energetic hot spot residues for mAb 225 binding to EGFR. These residues are adjacent to the EGFR ligand-binding site, which is consistent with the ability of mAb 225 to block binding of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) ligands. Ser468 and Glu472 were identified as energetically important for mAb 13A9 binding to EGFR, and the location of this epitope suggests that mAb 13A9 mediates observed TGF-alpha blocking effects through conformational perturbation of EGFR domain III. Combinatorial library screening of yeast-displayed mutagenic proteins is a novel method to identify discontinuous and heat-denaturable mAb binding epitopes with residue-level resolution. 相似文献
110.