全文获取类型
收费全文 | 936篇 |
免费 | 89篇 |
国内免费 | 9篇 |
出版年
2023年 | 4篇 |
2022年 | 8篇 |
2021年 | 24篇 |
2020年 | 6篇 |
2019年 | 10篇 |
2018年 | 9篇 |
2017年 | 10篇 |
2016年 | 22篇 |
2015年 | 36篇 |
2014年 | 48篇 |
2013年 | 39篇 |
2012年 | 76篇 |
2011年 | 57篇 |
2010年 | 38篇 |
2009年 | 32篇 |
2008年 | 35篇 |
2007年 | 55篇 |
2006年 | 36篇 |
2005年 | 34篇 |
2004年 | 38篇 |
2003年 | 28篇 |
2002年 | 31篇 |
2001年 | 43篇 |
2000年 | 27篇 |
1999年 | 14篇 |
1998年 | 5篇 |
1997年 | 11篇 |
1996年 | 9篇 |
1994年 | 7篇 |
1992年 | 21篇 |
1991年 | 24篇 |
1990年 | 20篇 |
1989年 | 16篇 |
1988年 | 14篇 |
1987年 | 20篇 |
1986年 | 9篇 |
1985年 | 15篇 |
1984年 | 6篇 |
1983年 | 9篇 |
1982年 | 9篇 |
1981年 | 8篇 |
1980年 | 6篇 |
1979年 | 13篇 |
1978年 | 5篇 |
1977年 | 4篇 |
1976年 | 11篇 |
1974年 | 6篇 |
1973年 | 5篇 |
1970年 | 4篇 |
1969年 | 4篇 |
排序方式: 共有1034条查询结果,搜索用时 31 毫秒
61.
Requirement for Pbx1 in skeletal patterning and programming chondrocyte proliferation and differentiation 总被引:14,自引:0,他引:14
Selleri L Depew MJ Jacobs Y Chanda SK Tsang KY Cheah KS Rubenstein JL O'Gorman S Cleary ML 《Development (Cambridge, England)》2001,128(18):3543-3557
Pbx1 and a subset of homeodomain proteins collaboratively bind DNA as higher-order molecular complexes with unknown consequences for mammalian development. Pbx1 contributions were investigated through characterization of Pbx1-deficient mice. Pbx1 mutants died at embryonic day 15/16 with severe hypoplasia or aplasia of multiple organs and widespread patterning defects of the axial and appendicular skeleton. An obligatory role for Pbx1 in limb axis patterning was apparent from malformations of proximal skeletal elements, but distal structures were unaffected. In addition to multiple rib and vertebral malformations, neural crest cell-derived skeletal structures of the second branchial arch were morphologically transformed into elements reminiscent of first arch-derived cartilages. Although the skeletal malformations did not phenocopy single or compound Hox gene defects, they were restricted to domains specified by Hox proteins bearing Pbx dimerization motifs and unaccompanied by alterations in Hox gene expression. In affected domains of limbs and ribs, chondrocyte proliferation was markedly diminished and there was a notable increase of hypertrophic chondrocytes, accompanied by premature ossification of bone. The pattern of expression of genes known to regulate chondrocyte differentiation was not perturbed in Pbx1-deficient cartilage at early days of embryonic skeletogenesis, however precocious expression of Col1a1, a marker of bone formation, was found. These studies demonstrate a role for Pbx1 in multiple developmental programs and reveal a novel function in co-ordinating the extent and/or timing of proliferation with terminal differentiation. This impacts on the rate of endochondral ossification and bone formation and suggests a mechanistic basis for most of the observed skeletal malformations. 相似文献
62.
63.
Gorczyca W Weisberger J Liu Z Tsang P Hossein M Wu CD Dong H Wong JY Tugulea S Dee S Melamed MR Darzynkiewicz Z 《Cytometry》2002,50(3):177-190
T-cell lymphoproliferative disorders are among the most challenging diagnoses in hematopathology. Unlike the more common B-cell disorders, in which clonality is often readily discernible by surface immunoglobulin light chain restriction, there is no specific immunophenotypic signature that is diagnostic of a clonal T-cell population. Immunophenotypic criteria that are helpful in the diagnosis of T-cell neoplasms include T-cell subset antigen restriction, anomalous T-cell subset antigen expression, deletion or diminution of one of the pan T-cell antigens, a precursor T-cell phenotype, and expression of additional markers (e.g., CD30, CD20, major myeloid antigens, and TCRgammadelta). Analysis of the inherent forward and orthogonal light scatter properties of the cell can also provide important diagnostic clues. None of these features is 100% specific, however, for aberrant expression of pan-T antigens may be seen in viral infections, B-cell malignancies, or in reactive changes following administration of certain medications. An increased CD4:CD8 ratio is often observed in Hodgkin's lymphoma. Based on the analysis of 87 neoplastic and 80 control cases, we conclude that flow cytometric features that are most suspicious for malignancy include the loss or markedly dim expression of CD45; complete loss of one or more pan-T antigens; diminished expression of more than two pan-T antigens in conjunction with altered light scatter properties; and CD4/CD8 dual-positive or dual-negative expression (except thymic lesions). 相似文献
64.
Growth and development rely on the mitochondrial respiratory chain (MRC) as the major source of ATP. We measured the mitochondrial DNA (mtDNA) copy number of each of the Caenorhabditis elegans developmental stages. Embryos, L1, L2, and L3 larvae all have approximately 25,000 copies of maternally derived mtDNA. The copy number increases fivefold in L4 larvae and a further sixfold in adult hermaphrodites, but only twofold in adult males. The majority of mtDNA in adult worms is germline associated, and germline-deficient mutants show markedly reduced mtDNA contents. With sperm-deficient or oocyte-deficient mutants, we confirm that mtDNA amplification is primarily associated with oocyte production. When mtDNA replication is inhibited, a quantitative and homogeneous arrest as L3 larvae occurs. Thus, mtDNA amplification is a necessary component of normal development and its regulation may involve an energy-sensing decision or checkpoint that can be invoked when mitochondrial energy generation is impaired. 相似文献
65.
66.
Matrix metalloproteinase-2 (MMP-2) is produced as a zymogen, which is subsequently activated by membrane-type 1 metalloproteinase (MT1-MMP). The objectives of the present study were to clone bovine MT1-MMP and to investigate its expression in the corpus luteum. Corpora lutea were harvested from nonlactating dairy cows on Days 4, 10, and 16 of the estrous cycle (Day 0 = estrus; n = 3 for each age). The bovine MT1-MMP cDNA contained an open reading frame of 1749 base pairs, which encoded a predicted protein of 582 amino acids. Northern blotting revealed no differences (P > 0.05) in MT1-MMP mRNA levels between any ages of corpora lutea. Western blotting demonstrated that two species of MT1-MMP, the latent form ( approximately 63 kDa) and the active form ( approximately 60 kDa), were present in corpora lutea throughout the estrous cycle. Active MT1-MMP was lower (P < 0.05) in early stages of the corpus luteum than the mid and late stages, where MMP-2 activity, as revealed by gelatin zymography, was also elevated. Furthermore, immunohistochemistry revealed that MT1-MMP was localized in endothelial, large luteal, and fibroblast cells of the corpus luteum at different stages. Taken together, the differential expression and localization of MT1-MMP in the corpus luteum suggest that it may have multiple functions throughout the course of the estrous cycle, including activation of pro-MMP-2. 相似文献
67.
Gensure RC Shimizu N Tsang J Gardella TJ 《Molecular endocrinology (Baltimore, Md.)》2003,17(12):2647-2658
Recent functional studies have suggested that position 19 in PTH interacts with the portion of the PTH-1 receptor (P1R) that contains the extracellular loops and seven transmembrance helices (TMs) (the J domain). We tested this hypothesis using the photoaffinity cross-linking approach. A PTHrP(1-36) analog and a conformationally constrained PTH(1-21) analog, each containing para-benzoyl-l-phenylalanine (Bpa) at position 19, each cross-linked efficiently to the P1R expressed in COS-7 cells, and digestive mapping analysis localized the cross-linked site to the interval (Leu232-Lys240) at the extracellular end of TM2. Point mutation analysis identified Ala234, Val235, and Lys240 as determinants of cross-linking efficiency, and the Lys240-->Ala mutation selectively impaired the binding of PTH(1-21) and PTH(1-19) analogs, relative to that of PTH(1-15) analogs. The findings support the hypothesis that residue 19 of the receptor-bound ligand contacts, or is close to, the P1R J domain-specifically, Lys240 at the extracellular end of TM2. The findings also support a molecular model in which the 1-21 region of PTH binds to the extracellular face of the P1R J domain as an alpha-helix. 相似文献
68.
69.
Tsang EW Yang J Chang Q Nowak G Kolenovsky A McGregor DI Keller WA 《Plant molecular biology》2003,51(2):191-201
Chlorophyll reduction in the seed of Brassica can be achieved by downregulating its synthesis. To reduce chlorophyll synthesis, we have used a cDNA clone of Brassica napus encoding glutamate 1-semialdehyde aminotransferase (GSA-AT) to make an antisense construct for gene manipulation. Antisense glutamate 1-semialdehyde aminotransferase gene (Gsa) expression, directed by a Brassica napin promoter, was targeted specifically to the embryo of the developing seed. Transformants expressing antisense Gsa showed varying degrees of inhibition resulting in a range of chlorophyll reduction in the seeds. Seed growth and development were not affected by reduction of chlorophyll. Seeds from selfed transgenic plants germinated with high efficiency and growth of seedlings was vigorous. Seedlings from T2 transgenic lines segregated into three distinctive phenotypes: dark green, light green and yellow, indicating the dominant inheritance of Gsa antisense gene. These transgenic lines have provided useful materials for the development of a low chlorophyll seed variety of B. napus. 相似文献
70.
Interactions between environmental and genetic factors in the pathophysiology of Parkinson's disease
Parkinson's disease (PD) is a progressive neurodegenerative disease with no known cure and affects approximately 1% of the elderly population. The major question in PD relates to the selective loss of dopaminergic neurons in patients. The underlying mechanism of genetic dysfunction and environmental toxins in contributing to the pathogenesis of PD may be oxidative stress. The interactions of genetic and environmental factors in PD may provide some answers to the longstanding question. In particular, the possibility that iron may provide selectivity to genetic susceptibility or dopamine reactivity in dopaminergic neuronal death is enhanced by the neuroprotection demonstrated in transgenic mice overexpressing ferritin or the use of iron chelators in MPTP-induced PD mouse. It will be important to dissect and understand the contributions of genes, environment and intrinsic cellular states in the generation and progression of the pathophysiology of PD. 相似文献