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51.
The differential cellular expression of class III beta-tubulin isotype (betaIII) is reviewed in the context of human embryological development and neoplasia. As compared to somatic organs and tissues, betaIII is abundant in the central and peripheral nervous systems (CNS and PNS) where it is prominently expressed during fetal and postnatal development. As exemplified in cerebellar and sympathoadrenal neurogenesis, the distribution of betaIII is neuron-associated, exhibiting distinct temporospatial gradients according to the regional neuroepithelia of origin. However, transient expression of this protein is also present in the subventricular zones of the CNS comprising putative neuronal- and/or glial precursor cells, as well as in Kulchitsky neuroendocrine cells of the fetal respiratory epithelium. This temporally restricted, potentially non-neuronal expression may have implications in the identification of presumptive neurons derived from embryonic stem cells. In adult tissues, the distribution of betaIII is almost exclusively neuron-specific. Altered patterns of expression are noted in cancer. In "embryonal"- and "adult-type" neuronal tumors of the CNS and PNS, betaIII is associated with neuronal differentiation and decreased cell proliferation. In contrast, the presence of betaIII in gliomas and lung cancer is associated with an ascending histological grade of malignancy. Thus, betaIII expression in neuronal tumors is differentiation-dependent, while in non-neuronal tumors it is aberrant and/or represents "dedifferentiation" associated with the acquisition of progenitor-like phenotypic properties. Increased expression in various epithelial cancer cell lines is associated with chemoresistance to taxanes. Because betaIII is present in subpopulations of neoplastic, but not in normal differentiated glial or somatic epithelial cells, the elucidation of mechanisms responsible for the altered expression of this isotype may provide insights into the role of the microtubule cytoskeleton in tumorigenesis and tumor progression. 相似文献
52.
Abdollahi A Gruver BN Patriotis C Hamilton TC 《Biochemical and biophysical research communications》2003,307(1):188-197
Alteration in epidermal growth factor receptor (EGFR) family signaling is among the most frequently implicated effectors of human oncogenesis. Overexpression of members of this family of receptors has often been detected in many epithelial tumors and is believed to be associated with an overall poor prognosis in patients with cancer. Therefore, we hypothesized that identification of potential EGF target genes in normal cells will provide a basis for unbiased genetic analysis of this signaling pathway in cancer. We utilized Atlas Rat 1.2 nylon cDNA arrays (Clontech) to determine gene expression changes in normal rat ovarian surface epithelial (ROSE) cells following EGF treatment. The results indicate activation of genes involved in a wide variety of cellular mechanisms, including regulation of cell cycle and proliferation, apoptosis, and protein turnover. In addition, using an in vitro model of ovarian cancer, we demonstrated that malignant transformation of ROSE cells resulted in alteration of downstream effectors of the EGFR pathway, as exemplified by aberrant expression of p66Shc, c-Jun, c-Myc, c-Fos, Lot1, p21Cip/Waf, and cdc25A. These data suggest that knowledge of the downstream genetic lesions, which may result in loss of growth factor requirement of the affected cells, will be crucial for the selection of the EGFR pathway as an effective target for cancer therapy. 相似文献
53.
Abatzopoulos Theodore J. El-Bermawi Nagy Vasdekis Christos Baxevanis Athanasios D. Sorgeloos Patrick 《Hydrobiologia》2003,492(1-3):191-199
An apomictic clone of the tetraploid parthenogenetic Artemia population from M. Embolon (Thessaloniki, Greece) was assayed for 10 reproductive and life span characteristics under laboratory conditions (in various salinity and temperature regimes). Salinity was proved to have significant impact on the majority of the characters used in this study. Discriminant function analysis gave an overall prediction of 97.32% over the three salinities (50, 80 and 120 ppt). The temperature of 30°C seemed to be an extreme one affecting significantly nearly all of the studied variables. The overall prediction according to the discriminant analysis was 94.69% among the three temperatures (22, 26 and 30°C). The clone performed best at 80 ppt and 22°C. The data presented in this study may generate useful suggestions to investigate the potentiality of using a single genetic lineage in order to visualize the effects of different environmental cues on a specific clone. 相似文献
54.
Is the Transportation Highway the Right Road for Hereditary Spastic Paraplegia? 总被引:13,自引:0,他引:13 下载免费PDF全文
The term "hereditary spastic paraplegia" (HSP) refers to a genetically and clinically diverse group of disorders whose primary feature is progressive spasticity of the lower extremities. The condition arises because of degeneration of the longest motor and sensory axons on the spinal cord, which appear to be most sensitive to the underlying mutations. The marked genetic heterogeneity in HSP, with 20 loci chromosomally mapped and eight genes now identified, suggests that a number of defective cellular processes may be shown to result in the disease. Although previous studies have suggested a mitochondrial basis for at least one form of the disease, a mechanism common to a number of the other genes mutated in HSP has remained elusive until now. The identification of the most recent genes for the condition suggests that aberrant cellular-trafficking dynamics may be a common process responsible for the specific pattern of neurodegeneration seen in HSP. 相似文献
55.
The role of ascorbic acid role in the differentiation of sclerotia in Sclerotinia minor 总被引:1,自引:0,他引:1
Sclerotinia minor in culture produces ascorbic acid in levels dependent on oxidative growth conditions and stage of development. During differentiation reduced/oxidized ascorbate ratio decreased by 12 and 6 fold at high and low oxidative stress, respectively. Exogenous ascorbate caused a concentration-dependent decrease of oxidative stress (lipid peroxidation), inhibition of sclerotial differentiation (up to 100%) and delay of differentiatlon (up to 10 days). Ascorbic acid may be produced to help the fungus reduce oxidative stress during growth. The data of this study support our theory proposing that oxidative stress is the inducing factor of sclerotial differentiation in fungi.This revised version was published online in October 2005 with corrections to the Cover Date. 相似文献
56.
Lipofuscins of lipidic and proteinaceous origin were identified by their excitation and emission spectra in phytopathogenic
fungal representatives of different sclerotial differentiation types. Lipofuscin pigments in Sclerotium rolfsii, Rhizoctonia solani, Sclerotinia minor and Sclerotinia sclerotiorum showed similar excitation and emission maxima (ex-em 330–450, 330–450, 330–470 and 3307–470 nm, respectively). Sclerotial
differentiation of these fungi was proceeded by a 4.2, 2.5, 2.7, 2.5 and 6, 2.9, 3.8, 3.1 fold increase of lipofuscin accumulation
(per lipid and protein content), per respective fungus, as compared to their undifferentiated stage. Lipofuscin levels were
higher in older than in younger mycelia and this phenomenon was more profound in S. rolfsii. Since lipofuscins are considered as indicators of oxidative stress, these data are in accordance with the hypothesis that
suggests oxidative stress to be a common underlying factor in sclerotial differentiation of sclerotia-forming filamentous
phytopathogenic fungi.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
57.
Pavlopoulos E Kokkinaki M Koutelou E Mitsiadis TA Prinos P Delidakis C Kilpatrick MW Tsipouras P Moschonas NK 《Biochimica et biophysica acta》2002,1574(3):375-382
The Drosophila neuralized (neur) gene belongs to the neurogenic group of genes involved in regulating cell-cell interactions required for neural precursor development. neur mutant phenotypes include strong overcommitment to neural fates at the expense of epidermal fates. The human neuralized homolog (NEURL) has been recently determined and found to map to chromosome 10q25.1 within the region frequently deleted in malignant astrocytomas. Because of its potential importance in developmental processes, we analyzed the structure of the mouse homolog, Neurl, and its expression pattern in embryonic tissues. Neurl activity is detected from early developmental stages in several tissues and organs including neural tissues, limbs, the skeletal system, sense organs and internal organs undergoing epithelial-mesenchymal interactions. Neurl encodes a polypeptide associated with the plasma membrane but also detected in the cytoplasm. Similarly to the Drosophila gene, mammalian neuralized may code for an important regulatory factor. 相似文献
58.
MOTIVATION: The field of bioinformatics has experienced an explosive growth in the last decade, yet this 'new' field has a long history. Some historical perspectives have been previously provided by the founders of this field. Here, we take the opportunity to review the early stages and follow developments of this discipline from a personal perspective. RESULTS: We review the early days of algorithmic questions and answers in biology, the theoretical foundations of bioinformatics, the development of algorithms and database resources and finally provide a realistic picture of what the field looked like from a resources and finally provide a realistic picture of what the field looked like from a practitioner's viewpoint 10 years ago, with a perspective for future developments. 相似文献
59.
Miederer M Seidl C Beyer GJ Charlton DE Vranjes-Duric S Comor JJ Huber R Nikula T Apostolidis C Schuhmacher C Becker KF Senekowitsch-Schmidtke R 《Radiation research》2003,159(5):612-620
We investigated the effects of the alpha-particle emitters (149)Tb and (213)Bi coupled to a tumor-specific antibody targeting the mutated delta 9 E-cadherin (d9 E-Cad) on single cells and cell pellets. The d9 mutation of the adhesion molecule E-cadherin is found in 10% of diffuse-type gastric cancers and is not expressed in normal tissue. Human breast cancer cells (MDA-MB-435S) transfected with d9 E-Cad or the wild-type E-cadherin gene were used to study the effects of anti-d9 E-Cad MAb coupled to (149)Tb and (213)Bi ((149)Tb-d9 MAb and (213)Bi-d9 MAb). The density of binding sites determined on transfected MDA tumor cells by Scatchard analysis and flow cytometry varied from 4 x 10(4) to 6 x 10(4) antigens per cell. Internalization of radioimmunoconjugates by cells expressing d9 E-Cad was less than 10% of bound antibody within 240 min. The effect of the radioimmunoconjugates on cell suspensions and cell pellets was quantified by [(3)H]thymidine incorporation, and the dose to the cell nuclei was determined using microdosimetric calculations. (149)Tb and (213)Bi immunoconjugates affected cells in suspension similarly. Significant differences in the proliferation capacity of d9 E-cadherin- and wild-type E-cadherin-expressing cells were observed at activity concentrations around 185 kBq/ml, corresponding to antibody concentrations between 200 ng/ml and 1000 ng/ml. Proliferation after incubation with (213)Bi-d9 MAb was 50% greater in pelleted wild-type E-Cad-expressing cells compared to wild-type E-Cad cells in suspension. In contrast, the proliferation of pelleted d9 E-Cad cells was similar to that of d9 E-Cad cells in suspension. For (149)Tb-d9 MAb, no significant difference was found between pelleted cells and cells in suspension for low activity concentrations. However, at high activity concentrations, (149)Tb-d9 MAb had only a small effect on pelleted cells. These in vitro studies demonstrate different effects of (149)Tb and (213)Bi conjugated to a tumor-specific antibody toward single cells and tumor cell pellets. Microdosimetric simulation of single cell survival after alpha-particle irradiation modeled the experimental results with reasonable accuracy. 相似文献
60.
Janssen P Audit B Cases I Darzentas N Goldovsky L Kunin V Lopez-Bigas N Peregrin-Alvarez JM Pereira-Leal JB Tsoka S Ouzounis CA 《Genome biology》2003,4(5):402-3
By the end of 2002, we witnessed the landmark submission of the 100th complete genome sequence in the databases. An overview of these genomes reveals certain interesting trends and provides valuable insights into possible future developments. 相似文献