全文获取类型
收费全文 | 374篇 |
免费 | 39篇 |
出版年
2021年 | 4篇 |
2019年 | 5篇 |
2018年 | 3篇 |
2017年 | 3篇 |
2016年 | 8篇 |
2015年 | 9篇 |
2014年 | 11篇 |
2013年 | 14篇 |
2012年 | 15篇 |
2011年 | 14篇 |
2010年 | 11篇 |
2009年 | 6篇 |
2008年 | 7篇 |
2007年 | 11篇 |
2006年 | 11篇 |
2005年 | 9篇 |
2004年 | 12篇 |
2003年 | 12篇 |
2002年 | 9篇 |
2001年 | 4篇 |
2000年 | 10篇 |
1999年 | 7篇 |
1998年 | 12篇 |
1997年 | 5篇 |
1996年 | 9篇 |
1995年 | 4篇 |
1994年 | 5篇 |
1993年 | 5篇 |
1992年 | 6篇 |
1990年 | 7篇 |
1989年 | 11篇 |
1986年 | 4篇 |
1985年 | 5篇 |
1984年 | 9篇 |
1983年 | 5篇 |
1982年 | 6篇 |
1980年 | 3篇 |
1979年 | 10篇 |
1978年 | 4篇 |
1977年 | 11篇 |
1976年 | 8篇 |
1975年 | 13篇 |
1974年 | 9篇 |
1973年 | 3篇 |
1972年 | 7篇 |
1971年 | 4篇 |
1970年 | 8篇 |
1957年 | 5篇 |
1950年 | 4篇 |
1949年 | 3篇 |
排序方式: 共有413条查询结果,搜索用时 515 毫秒
81.
Miguel Moreno-Azanza Blanca Bauluz José I. Canudo Eduardo Puértolas-Pascual Albert G. Sellés 《Historical Biology》2014,26(2):195-205
The Upper Cretaceous outcrops of the Pyrenees yield one of the most extensive and continuous records of paleoological remains anywhere in the world. Most of eggs and eggshells have been referred to the oofamily Megaloolithidae. In this study, we present a revision of eggshell fragments from the Blasi 2 locality, lattermost Maastrichtian in age, previously assigned to aff. Megaloolithidae. The presence of a blocky extinction pattern and basal knobs supports a crocodilian affinity of these materials. We classify them as Krokolithidae indet. Three structural layers can be recognised in the Blasi 2 eggshells, a feature that is shared with other recent eggshells (e.g. Crocodylus porosus and Crocodylus niloticus) and fossil crocodylomorph eggshells (Krokolitheswilsoni), which were previously described as single layered. The new proposed affinity of the Blasi 2 eggshells reduces the Megaloolithidae oodiversity of the last few million years of the Cretaceous in the Pyrenees to only two valid ootaxa, Megaloolithusmamillare and Megaloolithusbaghensis. The lack of more complete material precludes the erection of new ootaxa based on the Blasi 2 material. 相似文献
82.
VLJ Whitehall TD Dumenil DM McKeone CE Bond ML Bettington RL Buttenshaw L Bowdler GW Montgomery LF Wockner BA Leggett 《Epigenetics》2014,9(11):1454-1460
The CpG Island Methylator Phenotype (CIMP) is fundamental to an important subset of colorectal cancer; however, its cause is unknown. CIMP is associated with microsatellite instability but is also found in BRAF mutant microsatellite stable cancers that are associated with poor prognosis. The isocitrate dehydrogenase 1 (IDH1) gene causes CIMP in glioma due to an activating mutation that produces the 2-hydroxyglutarate oncometabolite. We therefore examined IDH1 alteration as a potential cause of CIMP in colorectal cancer. The IDH1 mutational hotspot was screened in 86 CIMP-positive and 80 CIMP-negative cancers. The entire coding sequence was examined in 81 CIMP-positive colorectal cancers. Forty-seven cancers varying by CIMP-status and IDH1 mutation status were examined using Illumina 450K DNA methylation microarrays. The R132C IDH1 mutation was detected in 4/166 cancers. All IDH1 mutations were in CIMP cancers that were BRAF mutant and microsatellite stable (4/45, 8.9%). Unsupervised hierarchical cluster analysis identified an IDH1 mutation-like methylation signature in approximately half of the CIMP-positive cancers. IDH1 mutation appears to cause CIMP in a small proportion of BRAF mutant, microsatellite stable colorectal cancers. This study provides a precedent that a single gene mutation may cause CIMP in colorectal cancer, and that this will be associated with a specific epigenetic signature and clinicopathological features. 相似文献
83.
The aim of the present study is to elucidate if Oxyporus philadelphi (Parmasto) Ryvarden and Botryodontia millavensis (Bourdot & Galzin) Duhem & H. Michel are conspecific, as suggested by their similar morphology. The analysis of ribosomal DNA ITS sequences indicate that the specimens of O. philadelphi and B. millavensis belong to a single species. The species is closely related to the type species (B. cirrata) of the genus Botryodontia, and therefore the name B. millavensis should currently be used for this taxon. Botryodontia millavensis grows on a wide selection of host species—Juniperus communis, Philadelphus coronarius, Picea abies, Fraxinus excelsior, Lonicera sp., J. turcomanica—and is distributed widely in temperate Eurasia. 相似文献
84.
Type 2 diabetes is a heterogeneous disease characterized by hyperglycemia and insulin resistance in peripheral tissues such as adipose tissue and skeletal muscle. This review focuses on obesity as one of the major environmental factors contributing to the development of diabetes. It has become evident that adipose tissue represents an active secretory organ capable of releasing a variety of cytokines such as TNFalpha, IL-6, adiponectin and other still unknown factors that might constitute the missing link between adipose tissue and insulin resistance. In fact, adipocyte-derived factors are significantly increased in obesity and represent good predictors of the development of type 2 diabetes. The negative crosstalk between adipocytes and skeletal muscle cells leads to disturbances in muscle cell insulin signalling and insulin resistance involving major pathways in inflammation, cellular stress and mitogenesis. Positive regulators of insulin sensitivity include the adipocyte hormone adiponectin and inhibitors of inflammatory pathways such as JNK-, IKK- and ERK-inhibitors. In summary, a better knowledge of intracellular and intercellular mechanisms by which adipose tissue affects skeletal muscle cell physiology may help to develop new strategies for diabetes treatment. 相似文献
85.
Taube A Schlich R Sell H Eckardt K Eckel J 《American journal of physiology. Heart and circulatory physiology》2012,302(11):H2148-H2165
Abdominal obesity is a major risk factor for cardiovascular disease, and recent studies highlight a key role of adipose tissue dysfunction, inflammation, and aberrant adipokine release in this process. An increased demand for lipid storage results in both hyperplasia and hypertrophy, finally leading to chronic inflammation, hypoxia, and a phenotypic change of the cellular components of adipose tissue, collectively leading to a substantially altered secretory output of adipose tissue. In this review we have assessed the adipo-vascular axis, and an overview of adipokines associated with cardiovascular disease is provided. This resulted in a first list of more than 30 adipokines. A deeper analysis only considered adipokines that have been reported to impact on inflammation and NF-κB activation in the vasculature. Out of these, the most prominent link to cardiovascular disease was found for leptin, TNF-α, adipocyte fatty acid-binding protein, interleukins, and several novel adipokines such as lipocalin-2 and pigment epithelium-derived factor. Future work will need to address the potential role of these molecules as biomarkers and/or drug targets. 相似文献
86.
Irena Bielańska-Grajner Anna Cudak Anna Biała Robert Szymańczak Jerzy Sell 《Limnology》2014,15(2):173-183
In spatially heterogeneous habitats, local communities may be shaped by both local biotic and abiotic factors and by regional factors (dispersal of individuals among habitats). In recent years, ecologists have been increasingly interested in measuring how much the structure of local communities is explained by spatial variables and by non-spatial environmental variables. We analysed the effects of biotic and abiotic factors on rotifer communities in 12 anthropogenic water bodies in the Silesian Upland. The studies were conducted in two groups of water bodies which were of differing dimensions: group A — seven water bodies situated very close to each other (between 50 and 500 m), group B — the water bodies from group A as well as 5 other water bodies situated 2 km away, which were at greater distances from each other (about 1–3 km). Apart from this, genetic variation was assessed in 3 populations of Brachionus plicatilis Müller to estimate the level of gene flow between them. A characteristic feature of anthropogenic water bodies is a high variation in environmental conditions, so they are specific and difficult habitats for many organisms. Our study shows that environmental factors played a major role in shaping the local rotifer communities in heterogeneous anthropogenic water bodies with respect to salinity. Results of this study suggest, however, that in neighbouring water bodies, dispersal is very important for maintenance of local species diversity. A medium level of genetic variation between populations of B. plicatilis indicates that gene flow occurs irrespective of the distance between local populations. 相似文献
87.
88.
Evolution of eutherian cytochrome c oxidase subunit II: heterogeneous rates of protein evolution and altered interaction with cytochrome c 总被引:3,自引:1,他引:2
Cytochrome c oxidase subunit II (COII), encoded by the mitochondrial
genome, exhibits one of the most heterogeneous rates of amino acid
replacement among placental mammals. Moreover, it has been demonstrated
that cytochrome c oxidase has undergone a structural change in higher
primates which has altered its physical interaction with cytochrome c. We
collected a large data set of COII sequences from several orders of mammals
with emphasis on primates, rodents, and artiodactyls. Using phylogenetic
hypotheses based on data independent of the COII gene, we demonstrated that
an increased number of amino acid replacements are concentrated among
higher primates. Incorporating approximate divergence dates derived from
the fossil record, we find that most of the change occurred independently
along the New World monkey lineage and in a rapid burst before apes and Old
World monkeys diverged. There is some evidence that Old World monkeys have
undergone a faster rate of nonsynonymous substitution than have apes. Rates
of substitution at four-fold degenerate sites in primates are relatively
homogeneous, indicating that the rate heterogeneity is restricted to
nondegenerate sites. Excluding the rate acceleration mentioned above,
primates, rodents, and artiodactyls have remarkably similar nonsynonymous
replacement rates. A different pattern is observed for transversions at
four-fold degenerate sites, for which rodents exhibit a higher rate of
replacement than do primates and artiodactyls. Finally, we hypothesize
specific amino acid replacements which may account for much of the
structural difference in cytochrome c oxidase between higher primates and
other mammals.
相似文献
89.
J Powell J Stone W C Chan Z D Yang A Leatherbury K W Sell W Wiktor-Jedrzejczak A Ahmed-Ansari 《Cellular immunology》1989,118(2):250-264
In vitro incubation of the erythroleukemic cell line K562 with interferon-gamma (IFN-gamma) renders these cells relatively resistant to natural killer (NK) cell lysis. However, such treatment does not alter their sensitivity to LAK cell lysis. Thus, the lytic susceptibility of interferon-gamma-treated K562 (I-K562) cells to LAK cells as opposed to its relative resistance to NK cell lysis provides a functional assay to help distinguish these two types of effector cells. The relative resistance of I-K562 for NK cell-mediated lysis was not secondary to the release of soluble factors or the frequency of Leu-19+, CD3+ T cells, residual IFN-gamma, or expression of MHC Class I molecules. Coincubation of I-K562 cells with NK or LAK cells overnight did not appreciably change the pattern of lytic responses against K562 and I-K562 target cells. However, incubation of PBMC in vitro with I-K562 but not native K562 in the presence of r-IL-2 leads to a marked decrease in the generation of LAK cells. The inhibition of LAK cell generation was not secondary to differences in the consumption of bioactive levels of IL-2. Differences in the lytic capability of NK and LAK effector cells suggest heterogeneity among cells that mediate such non-MHC-restricted lysis. Use was made of cells from a patient with a large granular lymphocyte lymphoproliferative disease (greater than 85% Leu-19+) to determine if such cells could be used to distinguish clonal population of cells which would represent NK or LAK cell function. Of interest was the finding that such cells, even after incubation in vitro with IL-2, showed lytic function representative of NK cells but not LAK cells. Data concerning the inhibition of LAK cell generation by I-K562 cells have important implications for future therapeutic trials of IFN-gamma and IL-2 in the treatment of human malignancies. 相似文献
90.
Effects of EDTA treatment upon the protein subunit composition and mechanical properties of mammalian single skeletal muscle fibers 总被引:9,自引:0,他引:9
下载免费PDF全文
![点击此处可从《The Journal of cell biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Considerable interest has been focused on the role of myosin light chain LC(2) in the contraction of vertebrate striated muscle. A study was undertaken to further our investigations (Moss, R.L., G.G. Giulian, and M.L. Greaser, 1981, J. Biol. Chem., 257:8588-8591) of the effects of LC(2) removal upon contraction in skinned fibers from rabbit psoas muscles. Isometric tension and maximum velocity of shortening, V(max), were measured in fiber segments prior to LC(2) removal. The segments were then bathed at 30 degrees C for up to 240 min in a buffer solution containing 20 mM EDTA in order to extract up to 60 percent of the LC(2). Troponin C (TnC) was also partially removed by this procedure. Mechanical measurements were done following the EDTA extraction and the readditions of first TnC and then LC(2) to the segments. The protein subunit compositions of the same fiber segments were determined following each of these procedures by SDS PAGE of small pieces of the fiber. V(max) was found to decrease as the LC(2) content of the fiber segments was reduced by increasing the duration of extraction. EDTA treatment also resulted in substantial reductions in tension due mainly to the loss of TnC, though smaller reductions due to the extraction of LC(2) were also observed. Reversal of the order of recombination of LC(2) and TnC indicated that the reduction in V(max) following EDTA treatment was a specific effect of LC(2) removal. These results strongly suggest that LC(2) may have roles in determining the kinetics and extent of interaction between myosin and actin. 相似文献