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141.
The water-soluble tetrazolium salt (WST-1) assay is frequently used to assess cell proliferation. However, our study showed that in normal and cancerous keratinocytes, this assay is more responsive to changes in oxygenation than to rates of cell growth. Stimulation of keratinocyte proliferation by low Ca2+ and suppression of proliferation by nocodazole resulted in modest changes in WST-1 readings, whereas gradually reducing the level of oxygen in the cellular environment from ambient (21%) to near anoxic (0.1%) revealed a very strong negative correlation between cell oxygenation and WST-1 reagent reduction. In contrast, the very similar MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] cell proliferation assay, which uses a different tetrazolium salt, showed no sensitivity to the level of oxygen. Unlike MTT, WST-1 reagent is reduced extracellularly through trans-plasma membrane transport (tPMET), thereby suggesting that tPMET is oxygen dependent. We propose that the WST-1 assay can be developed into a sensitive quantitative method to evaluate cell oxygenation in vitro and used to study the role of hypoxia and tPMET in homeostasis and disease (e.g., cancer). At the same time, WST-1 assay should be used cautiously to assess cell viability or proliferation because readings can be affected by certain extrinsic (low atmospheric oxygen or high density culture) or intrinsic (defects in oxygen-sensing pathways) factors. 相似文献
142.
William Roy Glass Lynda D. Corkum Nicholas E. Mandrak 《Environmental Biology of Fishes》2011,90(3):235-242
Spotted Gar (Lepisosteus oculatus), a species listed as Threatened under the Canadian Species at Risk Act (SARA) was collected during May and June, 2007 from several sites in Rondeau Bay, a shallow coastal wetland of Lake Erie. The first pectoral fin ray was removed from 78 individuals to age the fish and to determine individual growth characteristics. To assess the validity of using pectoral rays to age Spotted Gar, we compared techniques (otoliths, branchiostegal rays and pectoral rays) for ten individuals captured in southwestern Michigan. Agreement between readers and amongst the three structures was high; thus aging of Spotted Gar using sectioned pectoral rays is an effective method. Rondeau Bay specimens varied in age from 3 to 10 years and from 515 to 761 mm total length. Regression analysis of length vs. age data was calculated to be $ {\hbox{y}} = {19}.{\hbox{217x}} + {491}.{19}\left( {{{\hbox{R}}^{{2}}} = 0.{22}} \right) $ . The low R 2 value is attributed to having males and females, which differ in growth rates, combined. Growth rates of Rondeau Bay specimens were compared to a Louisiana population using ANCOVA. No significant difference was found in the rate of growth between these populations; however, condition was low as compared to a standard weight equation. This may lead to lower fecundity, contributing to the species?? rarity in Canada. 相似文献
143.
Otto SP Pannell JR Peichel CL Ashman TL Charlesworth D Chippindale AK Delph LF Guerrero RF Scarpino SV McAllister BF 《Trends in genetics : TIG》2011,27(9):358-367
Sex chromosomes differ from other chromosomes in the striking divergence they often show in size, structure, and gene content. Not only do they possess genes controlling sex determination that are restricted to either the X or Y (or Z or W) chromosomes, but in many taxa they also include recombining regions. In these 'pseudoautosomal regions' (PARs), sequence homology is maintained by meiotic pairing and exchange in the heterogametic sex. PARs are unique genomic regions, exhibiting some features of autosomes, but they are also influenced by their partial sex linkage. Here we review the distribution and structure of PARs among animals and plants, the theoretical predictions concerning their evolutionary dynamics, the reasons for their persistence, and the diversity and content of genes that reside within them. It is now clear that the evolution of the PAR differs in important ways from that of genes in either the non-recombining regions of sex chromosomes or the autosomes. 相似文献
144.
James EA DeVoti JA Rosenthal DW Hatam LJ Steinberg BM Abramson AL Kwok WW Bonagura VR 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(11):6633-6640
Recurrent respiratory papillomatosis (RRP) is caused by human papillomavirus type 6 (HPV-6) or HPV-11. Specific HLA-DR haplotypes DRB1*01:02 and DRB1*03:01 are associated with the development of RRP, disease severity, and Th2-like responses to HPV early proteins. Th1-like responses to HPV proteins have been shown to be protective in animal models. Therefore, we investigated the hypothesis that RRP patients have dysfunctional Th1-like, HPV-specific T cell responses. Using MHC class II tetramers, we identified immunogenic peptides within HPV-11 early proteins. Two distinct peptides (E6(113-132) and E2(1-20)) contained DRB1*01:02- or DRB1*03:01-restricted epitopes, respectively. An additional peptide (E2(281-300)) contained an epitope presented by both alleles. Peptide binding, tetramer, and proliferation assays identified minimal epitopes within these peptides. These epitopes elicited E2/E6-specific CD4(+) T cell responses in RRP patients and healthy control subjects, allowing the isolation of HPV-specific T cell lines using tetramers. The cytokine profiles and STAT signaling of these tetramer-positive T cells were measured to compare the polarization and responsiveness of HPV-specific T cells from patients with RRP and healthy subjects. HPV-specific IFN-γ secretion was substantially lower in T cells from RRP patients. HPV-specific IL-13 secretion was seen at modest levels in T cells from RRP patients and was absent in T cells from healthy control subjects. HPV-specific T cells from RRP patients exhibited reduced STAT-5 phosphorylation and reduced IL-2 secretion, suggesting anergy. Levels of STAT-5 phosphorylation and IFN-γ secretion could be improved through addition of IL-2 to HPV-specific T cell lines from RRP patients. Therapeutic vaccination or interventions aimed at restoring Th1-like cytokine responses to HPV proteins and reversing anergy could improve clinical outcomes for RRP patients. 相似文献
145.
Padidar S Farquharson AJ Williams LM Kelaiditi E Hoggard N Arthur JR Drew JE 《Journal of cellular physiology》2011,226(8):2123-2130
Dysregulation of leptin associated with obesity is implicated in obesity-related colon cancer, but mechanisms are elusive. Increased adiposity and elevated plasma leptin are associated with perturbed metabolism in colon and leptin receptors are expressed on colon epithelium. We hypothesise that obesity increases the sensitivity of the colon to cancer by disrupting leptin-regulated gene targets within colon tissues. PCR arrays were used to firstly identify leptin responsive genes and secondly to identify responses to leptin challenge in wild-type mice, or those lacking leptin (ob/ob). Leptin-regulated genes were localised in the colon using in situ hybridisation. IL6, IL1β and CXCL1 were up-regulated by leptin and localised to discrete cells in gut epithelium, lamina propria, muscularis and at the peritoneal serosal surface. Leptin regulates pro-inflammatory genes such as IL6, IL1β and CXCL1, and might increase the risk of colon cancer among obese individuals. 相似文献
146.
Animals were given five cycles of an activity anorexia (AA) procedure in order to determine the effect of additional experience on eating, running, and weight loss. Female Sprague-Dawley rats were given a 1h meal and allowed access to a running wheel for the remainder of each day. Upon reaching 75% of free-feeding body weight, each animal was denied wheel access and given ad libitum food until it regained the lost weight. Then, food was again restricted and wheel access provided. Sedentary control animals were placed on the restricted feeding schedule for the median number of days experimental animals required to reach weight loss criterion. Experimental animals showed adaptation by increasing food consumption and decreasing the rate of weight loss despite an increase in running across cycles. Additionally, the distribution of running shifted gradually so that during the later cycles, much of the running occurred in the hours just before feeding. The results support the hypothesis that running interferes with adaptation to the restricted feeding schedule and also that the marked increase in anticipatory behavior during the later cycles is primarily responsible for the maintenance of AA. 相似文献
147.
148.
Lynda M Groocock Minghua Nie John Prudden Davide Moiani Tao Wang Anton Cheltsov Robert P Rambo Andrew S Arvai Chiharu Hitomi John A Tainer Karolin Luger J Jefferson P Perry Eros Lazzerini‐Denchi Michael N Boddy 《EMBO reports》2014,15(5):601-608
The post‐translational modification of DNA repair and checkpoint proteins by ubiquitin and small ubiquitin‐like modifier (SUMO) critically orchestrates the DNA damage response (DDR). The ubiquitin ligase RNF4 integrates signaling by SUMO and ubiquitin, through its selective recognition and ubiquitination of SUMO‐modified proteins. Here, we define a key new determinant for target discrimination by RNF4, in addition to interaction with SUMO. We identify a nucleosome‐targeting motif within the RNF4 RING domain that can bind DNA and thereby enables RNF4 to selectively ubiquitinate nucleosomal histones. Furthermore, RNF4 nucleosome‐targeting is crucially required for the repair of TRF2‐depleted dysfunctional telomeres by 53BP1‐mediated non‐homologous end joining. 相似文献
149.
Stéphanie Cornen Arnaud Guille José Adéla?de Lynda Addou-Klouche Pascal Finetti Marie-Rose Saade Marwa Manai Nadine Carbuccia Ismahane Bekhouche Anne Letessier Stéphane Raynaud Emmanuelle Charafe-Jauffret Jocelyne Jacquemier Salvatore Spicuglia Hugues de The Patrice Viens Fran?ois Bertucci Daniel Birnbaum Max Chaffanet 《PloS one》2014,9(1)
Breast cancers (BCs) of the luminal B subtype are estrogen receptor-positive (ER+), highly proliferative, resistant to standard therapies and have a poor prognosis. To better understand this subtype we compared DNA copy number aberrations (CNAs), DNA promoter methylation, gene expression profiles, and somatic mutations in nine selected genes, in 32 luminal B tumors with those observed in 156 BCs of the other molecular subtypes. Frequent CNAs included 8p11-p12 and 11q13.1-q13.2 amplifications, 7q11.22-q34, 8q21.12-q24.23, 12p12.3-p13.1, 12q13.11-q24.11, 14q21.1-q23.1, 17q11.1-q25.1, 20q11.23-q13.33 gains and 6q14.1-q24.2, 9p21.3-p24,3, 9q21.2, 18p11.31-p11.32 losses. A total of 237 and 101 luminal B-specific candidate oncogenes and tumor suppressor genes (TSGs) presented a deregulated expression in relation with their CNAs, including 11 genes previously reported associated with endocrine resistance. Interestingly, 88% of the potential TSGs are located within chromosome arm 6q, and seven candidate oncogenes are potential therapeutic targets. A total of 100 candidate oncogenes were validated in a public series of 5,765 BCs and the overexpression of 67 of these was associated with poor survival in luminal tumors. Twenty-four genes presented a deregulated expression in relation with a high DNA methylation level. FOXO3, PIK3CA and TP53 were the most frequent mutated genes among the nine tested. In a meta-analysis of next-generation sequencing data in 875 BCs, KCNB2 mutations were associated with luminal B cases while candidate TSGs MDN1 (6q15) and UTRN (6q24), were mutated in this subtype. In conclusion, we have reported luminal B candidate genes that may play a role in the development and/or hormone resistance of this aggressive subtype. 相似文献
150.
Lynda M. Williams Fiona M. Campbell Janice E. Drew Christiane Koch Nigel Hoggard William D. Rees Torkamol Kamolrat Ha Thi Ngo Inger-Lise Steffensen Stuart R. Gray Alexander Tups 《PloS one》2014,9(8)
High–fat (HF) diet-induced obesity and insulin insensitivity are associated with inflammation, particularly in white adipose tissue (WAT). However, insulin insensitivity is apparent within days of HF feeding when gains in adiposity and changes in markers of inflammation are relatively minor. To investigate further the effects of HF diet, C57Bl/6J mice were fed either a low (LF) or HF diet for 3 days to 16 weeks, or fed the HF-diet matched to the caloric intake of the LF diet (PF) for 3 days or 1 week, with the time course of glucose tolerance and inflammatory gene expression measured in liver, muscle and WAT. HF fed mice gained adiposity and liver lipid steadily over 16 weeks, but developed glucose intolerance, assessed by intraperitoneal glucose tolerance tests (IPGTT), in two phases. The first phase, after 3 days, resulted in a 50% increase in area under the curve (AUC) for HF and PF mice, which improved to 30% after 1 week and remained stable until 12 weeks. Between 12 and 16 weeks the difference in AUC increased to 60%, when gene markers of inflammation appeared in WAT and muscle but not in liver. Plasma proteomics were used to reveal an acute phase response at day 3. Data from PF mice reveals that glucose intolerance and the acute phase response are the result of the HF composition of the diet and increased caloric intake respectively. Thus, the initial increase in glucose intolerance due to a HF diet occurs concurrently with an acute phase response but these effects are caused by different properties of the diet. The second increase in glucose intolerance occurs between 12 - 16 weeks of HF diet and is correlated with WAT and muscle inflammation. Between these times glucose tolerance remains stable and markers of inflammation are undetectable. 相似文献