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871.
Meyer B Bazzi H Zidek V Musilova A Pravenec M Kurtz TW Nurnberg P Christiano AM 《Differentiation; research in biological diversity》2004,72(9-10):541-547
A recessive hairless mutation arose spontaneously in a congenic line of spontaneously hypertensive rats SHR.BN-(D1Mit3-Igf2)/Ipcv. The mutant rats develop generalized alopecia except for partial hair growth on their heads. Affected animals of the congenic line were crossed with LEW rats and randomly bred for several generations. A genome scan in 74 affected and 75 unaffected offspring localized the mutant gene on rat chromosome 18p12, near the marker D18Rat107, which is closely linked to the desmosomal cadherin gene cluster, syntenic to mouse chromosome 18 and human chromosome 18q12. Recently, the mouse and rat phenotypes lah/lah (lanceolate hair) and lah(J)/lah(J)(lanceolate hair-J) were found to be caused by mutations in the desmoglein 4 (Dsg4) gene. Direct sequencing of the Dsg4 gene in the SHR revealed a homozygous C-to-T transition generating a premature termination codon within exon 8 in the affected animals. Further studies on the skin histology in affected rats demonstrated features consistent with a lanceolate hair mutation, providing further support for the crucial role of desmoglein 4 in hair shaft differentiation. 相似文献
872.
873.
Olszewski PK Rozman J Jacobsson JA Rathkolb B Strömberg S Hans W Klockars A Alsiö J Risérus U Becker L Hölter SM Elvert R Ehrhardt N Gailus-Durner V Fuchs H Fredriksson R Wolf E Klopstock T Wurst W Levine AS Marcus C de Angelis MH Klingenspor M Schiöth HB Kilimann MW 《PLoS genetics》2012,8(3):e1002568
Neurobeachin (Nbea) regulates neuronal membrane protein trafficking and is required for the development and functioning of central and neuromuscular synapses. In homozygous knockout (KO) mice, Nbea deficiency causes perinatal death. Here, we report that heterozygous KO mice haploinsufficient for Nbea have higher body weight due to increased adipose tissue mass. In several feeding paradigms, heterozygous KO mice consumed more food than wild-type (WT) controls, and this consumption was primarily driven by calories rather than palatability. Expression analysis of feeding-related genes in the hypothalamus and brainstem with real-time PCR showed differential expression of a subset of neuropeptide or neuropeptide receptor mRNAs between WT and Nbea+/- mice in the sated state and in response to food deprivation, but not to feeding reward. In humans, we identified two intronic NBEA single-nucleotide polymorphisms (SNPs) that are significantly associated with body-mass index (BMI) in adult and juvenile cohorts. Overall, data obtained in mice and humans suggest that variation of Nbea abundance or activity critically affects body weight, presumably by influencing the activity of feeding-related neural circuits. Our study emphasizes the importance of neural mechanisms in body weight control and points out NBEA as a potential risk gene in human obesity. 相似文献
874.
Successful filler dispersion and establishment of good interfacial contact with the surrounding matrix are essential for optimized reinforcement in polymeric nanocomposites. In particular, in renewable-based composites this can be challenging, where hydrophilic attractions between nanofillers facilitate aggregation. Here an innovative approach to prepare cellulosic nanowhisker (CNW) reinforced polylactide (PLA) is presented. The lactide ring-opening polymerization is initiated from CNW surface hydroxyl groups after partial acetylation to control the grafting density. Grafting of PLA chains is verified by Fourier transform infrared spectroscopy. The resulting nanocomposites display exceptional properties; a heat distortion temperature of 120 °C is achieved at 10 wt % CNW loading and can be further enhanced to reach 150 °C at 15 wt % CNW. The formation of a percolating network is verified by comparison of modulus data with an established theoretical model. Additionally, nucleation by CNWs reduces the crystallization half-time to 15 s compared with 90 s for PLA. Melt-pressed films retain transparency indicating good filler dispersion. 相似文献
875.
Schilling B Rardin MJ MacLean BX Zawadzka AM Frewen BE Cusack MP Sorensen DJ Bereman MS Jing E Wu CC Verdin E Kahn CR Maccoss MJ Gibson BW 《Molecular & cellular proteomics : MCP》2012,11(5):202-214
Despite advances in metabolic and postmetabolic labeling methods for quantitative proteomics, there remains a need for improved label-free approaches. This need is particularly pressing for workflows that incorporate affinity enrichment at the peptide level, where isobaric chemical labels such as isobaric tags for relative and absolute quantitation and tandem mass tags may prove problematic or where stable isotope labeling with amino acids in cell culture labeling cannot be readily applied. Skyline is a freely available, open source software tool for quantitative data processing and proteomic analysis. We expanded the capabilities of Skyline to process ion intensity chromatograms of peptide analytes from full scan mass spectral data (MS1) acquired during HPLC MS/MS proteomic experiments. Moreover, unlike existing programs, Skyline MS1 filtering can be used with mass spectrometers from four major vendors, which allows results to be compared directly across laboratories. The new quantitative and graphical tools now available in Skyline specifically support interrogation of multiple acquisitions for MS1 filtering, including visual inspection of peak picking and both automated and manual integration, key features often lacking in existing software. In addition, Skyline MS1 filtering displays retention time indicators from underlying MS/MS data contained within the spectral library to ensure proper peak selection. The modular structure of Skyline also provides well defined, customizable data reports and thus allows users to directly connect to existing statistical programs for post hoc data analysis. To demonstrate the utility of the MS1 filtering approach, we have carried out experiments on several MS platforms and have specifically examined the performance of this method to quantify two important post-translational modifications: acetylation and phosphorylation, in peptide-centric affinity workflows of increasing complexity using mouse and human models. 相似文献
876.
B Lohberger B Rinner N Stuendl M Absenger B Liegl-Atzwanger SM Walzer R Windhager A Leithner 《PloS one》2012,7(8):e43664
Tumors contain a small population of cancer stem cells (CSC) proposed to be responsible for tumor maintenance and relapse. Aldehyde dehydrogenase 1 (ALDH1) activity has been used as a functional stem cell marker to isolate CSCs in different cancer types. This study used the Aldefluor® assay and fluorescence-activated cell sorting (FACS) analysis to isolate ALDH1high cells from five human sarcoma cell lines and one primary chordoma cell line. ALDH1high cells range from 0.3% (MUG-Chor1) to 4.1% (SW-1353) of gated cells. Immunohistochemical staining, analysis of the clone formation efficiency, and xCELLigence microelectronic sensor technology revealed that ALDH1high cells from all sarcoma cell lines have an increased proliferation rate compared to ALDH1low cells. By investigating of important regulators of stem cell biology, real-time RT-PCR data showed an increased expression of c-Myc, β-catenin, and SOX-2 in the ALDH1high population and a significant higher level of ABCG2. Statistical analysis of data demonstrated that ALDH1high cells of SW-982 and SW-1353 showed higher resistance to commonly used chemotherapeutic agents like doxorubicin, epirubicin, and cisplatin than ALDH1low cells. This study demonstrates that in different sarcoma cell lines, high ALDH1 activity can be used to identify a subpopulation of cells characterized by a significantly higher proliferation rate, increased colony forming, increased expression of ABC transporter genes and stemness markers compared to control cells. In addition, enhanced drug resistance was demonstrated. 相似文献
877.
Schillinger C Petrich A Lux R Riep B Kikhney J Friedmann A Wolinsky LE Göbel UB Daims H Moter A 《PloS one》2012,7(5):e37583
The polymicrobial nature of periodontal diseases is reflected by the diversity of phylotypes detected in subgingival plaque and the finding that consortia of suspected pathogens rather than single species are associated with disease development. A number of these microorganisms have been demonstrated in vitro to interact and enhance biofilm integration, survival or even pathogenic features. To examine the in vivo relevance of these proposed interactions, we extended the spatial arrangement analysis tool of the software daime (digital image analysis in microbial ecology). This modification enabled the quantitative analysis of microbial co-localization in images of subgingival biofilm species, where the biomass was confined to fractions of the whole-image area, a situation common for medical samples. Selected representatives of the disease-associated red and orange complexes that were previously suggested to interact with each other in vitro (Tannerella forsythia with Fusobacterium nucleatum and Porphyromonas gingivalis with Prevotella intermedia) were chosen for analysis and labeled with specific fluorescent probes via fluorescence in situ hybridization. Pair cross-correlation analysis of in vivo grown biofilms revealed tight clustering of F. nucleatum/periodonticum and T. forsythia at short distances (up to 6 μm) with a pronounced peak at 1.5 μm. While these results confirmed previous in vitro observations for F. nucleatum and T. forsythia, random spatial distribution was detected between P. gingivalis and P. intermedia in the in vivo samples. In conclusion, we successfully employed spatial arrangement analysis on the single cell level in clinically relevant medical samples and demonstrated the utility of this approach for the in vivo validation of in vitro observations by analyzing statistically relevant numbers of different patients. More importantly, the culture-independent nature of this approach enables similar quantitative analyses for "as-yet-uncultured" phylotypes which cannot be characterized in vitro. 相似文献
878.
Braem MG Onland-Moret NC Schouten LJ Kruitwagen RF Lukanova A Allen NE Wark PA Tjønneland A Hansen L Braüner CM Overvad K Clavel-Chapelon F Chabbert-Buffet N Teucher B Floegel A Boeing H Trichopoulou A Adarakis G Plada M Rinaldi S Fedirko V Romieu I Pala V Galasso R Sacerdote C Palli D Tumino R Bueno-de-Mesquita HB Gram IT Gavrilyuk O Lund E Sánchez MJ Bonet C Chirlaque MD Larrañaga N Gurrea AB Quirós JR Idahl A Ohlson N Lundin E Jirström K Butt S Tsilidis KK Khaw KT Wareham N Riboli E Kaaks R 《PloS one》2012,7(5):e37141
While the risk of ovarian cancer clearly reduces with each full-term pregnancy, the effect of incomplete pregnancies is unclear. We investigated whether incomplete pregnancies (miscarriages and induced abortions) are associated with risk of epithelial ovarian cancer. This observational study was carried out in female participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 274,442 women were followed from 1992 until 2010. The baseline questionnaire elicited information on miscarriages and induced abortions, reproductive history, and lifestyle-related factors. During a median follow-up of 11.5 years, 1,035 women were diagnosed with incident epithelial ovarian cancer. Despite the lack of an overall association (ever vs. never), risk of ovarian cancer was higher among women with multiple incomplete pregnancies (HR(≥4vs.0): 1.74, 95% CI: 1.20-2.70; number of cases in this category: n?=?23). This association was particularly evident for multiple miscarriages (HR(≥4vs.0): 1.99, 95% CI: 1.06-3.73; number of cases in this category: n?=?10), with no significant association for multiple induced abortions (HR(≥4vs.0): 1.46, 95% CI: 0.68-3.14; number of cases in this category: n?=?7). Our findings suggest that multiple miscarriages are associated with an increased risk of epithelial ovarian cancer, possibly through a shared cluster of etiological factors or a common underlying pathology. These findings should be interpreted with caution as this is the first study to show this association and given the small number of cases in the highest exposure categories. 相似文献
879.
880.
Daniel?LauterbachEmail author Michael?Ristow Birgit?Gemeinholzer 《Plant Systematics and Evolution》2012,298(1):155-164
Population fragmentation is often correlated with loss of genetic diversity and reduced fitness. Obligate out-crossing (dioecy)
is expected to enhance genetic diversity, reduce genetic differentiation, and avoid inbreeding depression through frequent
gene flow. However, in highly fragmented populations dioecy has only diminishing effects upon genetic structure as pollination
limitations (e.g. flight distance of pollinators) most often restrict inter-population gene flow in insect pollinated species.
In fragmented dry grasslands in northeastern Germany, we analysed genetic structure, fitness, and habitat quality of the endangered
dioecious Silene otites (Caryophyllaceae). Using AFLP markers, a high level of differentiation among ten populations was found (F
st = 0.36), while the intra-population genetic diversities (H
E = 0.165–0.240) were similar as compared to hermaphroditic species. There was neither a correlation between geographic and
genetic distance nor between genetic diversity and population size, which indicates reduced gene flow among populations and
random genetic drift. Plant size was positively correlated with genetic diversity. Seed set and number of juveniles were positively
related to population size. Higher total coverage resulted in reduced plant fitness, and the number of juveniles was negatively
correlated to cryptogam cover. Additionally, we found a sex ratio bias towards more male plants in larger populations. Overall,
our results indicate that on a regional geographic scale dioecy does not necessarily prevent genetic erosion in the case
of habitat fragmentation, especially in the absence of long distance seed and pollen dispersal capacity. 相似文献