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991.
Mesel-Lemoine M Millet J Vidalain PO Law H Vabret A Lorin V Escriou N Albert ML Nal B Tangy F 《Journal of virology》2012,86(14):7577-7587
Human coronaviruses are associated with upper respiratory tract infections that occasionally spread to the lungs and other organs. Although airway epithelial cells represent an important target for infection, the respiratory epithelium is also composed of an elaborate network of dendritic cells (DCs) that are essential sentinels of the immune system, sensing pathogens and presenting foreign antigens to T lymphocytes. In this report, we show that in vitro infection by human coronavirus 229E (HCoV-229E) induces massive cytopathic effects in DCs, including the formation of large syncytia and cell death within only few hours. In contrast, monocytes are much more resistant to infection and cytopathic effects despite similar expression levels of CD13, the membrane receptor for HCoV-229E. While the differentiation of monocytes into DCs in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4 requires 5 days, only 24 h are sufficient for these cytokines to sensitize monocytes to cell death and cytopathic effects when infected by HCoV-229E. Cell death induced by HCoV-229E is independent of TRAIL, FasL, tumor necrosis factor alpha, and caspase activity, indicating that viral replication is directly responsible for the observed cytopathic effects. The consequence of DC death at the early stage of HCoV-229E infection may have an impact on the early control of viral dissemination and on the establishment of long-lasting immune memory, since people can be reinfected multiple times by HCoV-229E. 相似文献
992.
Fan B Dachrut S Coral H Yuen ST Chu KM Law S Zhang L Ji J Leung SY Chen X 《PloS one》2012,7(4):e29824
Background
Genomic instability with frequent DNA copy number alterations is one of the key hallmarks of carcinogenesis. The chromosomal regions with frequent DNA copy number gain and loss in human gastric cancer are still poorly defined. It remains unknown how the DNA copy number variations contributes to the changes of gene expression profiles, especially on the global level.Principal Findings
We analyzed DNA copy number alterations in 64 human gastric cancer samples and 8 gastric cancer cell lines using bacterial artificial chromosome (BAC) arrays based comparative genomic hybridization (aCGH). Statistical analysis was applied to correlate previously published gene expression data obtained from cDNA microarrays with corresponding DNA copy number variation data to identify candidate oncogenes and tumor suppressor genes. We found that gastric cancer samples showed recurrent DNA copy number variations, including gains at 5p, 8q, 20p, 20q, and losses at 4q, 9p, 18q, 21q. The most frequent regions of amplification were 20q12 (7/72), 20q12–20q13.1 (12/72), 20q13.1–20q13.2 (11/72) and 20q13.2–20q13.3 (6/72). The most frequent deleted region was 9p21 (8/72). Correlating gene expression array data with aCGH identified 321 candidate oncogenes, which were overexpressed and showed frequent DNA copy number gains; and 12 candidate tumor suppressor genes which were down-regulated and showed frequent DNA copy number losses in human gastric cancers. Three networks of significantly expressed genes in gastric cancer samples were identified by ingenuity pathway analysis.Conclusions
This study provides insight into DNA copy number variations and their contribution to altered gene expression profiles during human gastric cancer development. It provides novel candidate driver oncogenes or tumor suppressor genes for human gastric cancer, useful pathway maps for the future understanding of the molecular pathogenesis of this malignancy, and the construction of new therapeutic targets. 相似文献993.
In the current study, we examined the potential significance of CD44 expression on lymphokine-activated killer (LAK) cells
in their interaction and killing of melanoma cells. Stimulation of splenocytes with IL-2 led to a significant increase in
the expression of CD44 on T cells, NK cells, and NKT cells. Treatment of melanoma-bearing CD44 WT mice with IL-2 led to a
significant reduction in the local tumor growth while treatment of melanoma-bearing CD44 KO mice with IL-2 was ineffective
at controlling tumor growth. Furthermore, the ability of splenocytes from IL-2-treated CD44 KO mice to kill melanoma tumor
targets was significantly reduced when compared to the anti-tumor activity of splenocytes from IL-2-treated CD44 WT mice.
The importance of CD44 expression on the LAK cells was further confirmed by the observation that adoptively transferred CD44
WT LAK cells were significantly more effective than CD44 KO LAK cells at controlling tumor growth in vivo. Next, the significance
of the increased expression of CD44 in tumor killing was examined and showed that following stimulation with IL-2, distinct
populations of cells with low (CD44lo) or elevated (CD44hi) expression of CD44 are generated and that the CD44hi cells are responsible for killing of the melanoma cells. The reduced killing activity of the CD44 KO LAK cells did not result
from reduced activation or expression of effector molecules but was due, at least in part, to a reduced ability to adhere
to B16F10 tumor cells. 相似文献
994.
DNA complementary to mouse yolk sac messenger RNA has been inserted at the PstI site of the plasmid pBR322 by annealing of the oligo(dG)-tailed plasmid DNA with the oligo(dC)-tailed mouse DNA. Transformation of Escherichia coli strain RRI with this annealed DNA yielded clones bearing recombinant plasmids. The clones were screened for DNA complementary to mouse a-fetoprotein (AFP) messenger RNA sequences by hybridization with a cDNA probe transcribed from an AFP mRNA of over 90% purity. Out of nine plasmids that were isolated and analyzed by restriction mapping, all had homologous insert DNA of various lengths. The plasmid with the longest insert, pAF6, contained 1.65 kb of added DNA, which is about 70% of the AFP mRNA. This clone was positively identified by a hybridization-translation procedure to contain a cDNA sequence for AFP. A restriction map of this clone and the orientation of the message are presented. 相似文献
995.
996.
Norman BH Gruber JM Hollinshead SP Wilson JW Starling JJ Law KL Self TD Tabas LB Williams DC Paul DC Wagner MM Dantzig AH 《Bioorganic & medicinal chemistry letters》2002,12(6):883-886
Tricyclic isoxazoles were identified from a screen as a novel class of selective multidrug resistance protein (MRP1) inhibitors. From a screen lead, SAR efforts resulted in the preparation of LY 402913 (9h), which inhibits MRP1 and reverses drug resistance to MRP1 substrates, such as doxorubicin, in HeLa-T5 cells (EC(50)=0.90 microM), while showing no inherent cytotoxicity. Additionally, LY 402913 inhibits ATP-dependent, MRP1-mediated LTC(4) uptake into membrane vesicles prepared from the MRP1-overexpressing HeLa-T5 cells (EC(50)=1.8 microM). LY 402913 also shows selectivity ( approximately 22-fold) against the related transporter, P-glycoprotein, in HL60/Adr and HL60/Vinc cells. Finally, when dosed in combination with the oncolytic MRP1 substrate vincristine, LY 402913 delays the growth of MRP1-overexpressing tumors in vivo. 相似文献
997.
Background
Self-medication with antibiotics (SMA) has been reported among university students in many countries, but little research has been done on this issue in China. The objective of this study was to evaluate knowledge and behaviors of university students and risk factors concerning SMA.Methodology/Principal Findings
Using a novel questionnaire-based data collection instrument, an anonymous online survey was conducted with the students of Shantou University (STU), a university comprising 8 schools/colleges in eastern Guangdong, China. Of 1,300 respondents (13.8% of total eligible participants), 47.8% had self-treated with antibiotics. Logistic regression analysis identified prior knowledge of antibiotics (PKA), older age, and higher monthly allowance as independent risk factors for SMA. PKA significantly influenced students'' knowledge about antibiotics, their uses, and common adverse reactions (all p<0.05). Among self-medicated students, 61.7% used antibiotics at least twice in the previous year. Community pharmacies were the major source of self-prescribed antibiotics. Reported common indications for SMA were sore throat (59.7%), fever (38.2%), cough (37.4%), runny nose (29.3%), and nasal congestion (28.7%). While 74.1% of self-medication episodes were based on students'' own experiences, only 31.1% of students claimed to understand the package insert. Alteration of antibiotics and dosage during the course of self-treatment was made by 63.8% and 55.6% of students, respectively. At least two kinds of antibiotics were simultaneously taken by 82.6% of students. The majority of self-medicated students failed to complete the course of antibiotics. Adverse reactions were reported by 16.3% of students. Amoxicillin was the most common antibiotic used for self-medication.Conclusions
High prevalence of SMA was noted among STU students. Presence of risk factors and risk-associated behaviors/attitudes in the study population calls for focused educational intervention and stricter governmental legislation and regulation of antibiotic use and sale in pharmacies. 相似文献998.
Tang HL Tang HM Mak KH Hu S Wang SS Wong KM Wong CS Wu HY Law HT Liu K Talbot CC Lau WK Montell DJ Fung MC 《Molecular biology of the cell》2012,23(12):2240-2252
Apoptosis serves as a protective mechanism by eliminating damaged cells through programmed cell death. After apoptotic cells pass critical checkpoints, including mitochondrial fragmentation, executioner caspase activation, and DNA damage, it is assumed that cell death inevitably follows. However, this assumption has not been tested directly. Here we report an unexpected reversal of late-stage apoptosis in primary liver and heart cells, macrophages, NIH 3T3 fibroblasts, cervical cancer HeLa cells, and brain cells. After exposure to an inducer of apoptosis, cells exhibited multiple morphological and biochemical hallmarks of late-stage apoptosis, including mitochondrial fragmentation, caspase-3 activation, and DNA damage. Surprisingly, the vast majority of dying cells arrested the apoptotic process and recovered when the inducer was washed away. Of importance, some cells acquired permanent genetic changes and underwent oncogenic transformation at a higher frequency than controls. Global gene expression analysis identified a molecular signature of the reversal process. We propose that reversal of apoptosis is an unanticipated mechanism to rescue cells from crisis and propose to name this mechanism "anastasis" (Greek for "rising to life"). Whereas carcinogenesis represents a harmful side effect, potential benefits of anastasis could include preservation of cells that are difficult to replace and stress-induced genetic diversity. 相似文献
999.
Law Smith MJ Deady DK Moore FR Jones BC Cornwell RE Stirrat M Lawson JF Feinberg DR Perrett DI 《Hormones and behavior》2012,61(1):12-16
Previous studies have shown that women with higher maternal tendencies are shorter and have lower testosterone levels than those with lower maternal tendencies. Here we report two studies that investigated the relationships between maternal tendencies and two further measures of physical masculinization/feminization; urinary estrogen metabolite (estrone-3-glucuronide: E1-3G) levels (Study 1) and rated facial femininity (Study 2). In Study 1, nulliparous women reported both their ideal number of children and ideal own age at first child and also provided urine samples. There was a significant positive correlation between measured late-follicular estrogen levels and reported ideal number of children. In Study 2, analyses of facial cues in two independent samples of women showed that the average facial characteristics of women who reported desiring many children were rated as more feminine than those desiring fewer children. Collectively, these results support the proposal that maternal tendencies are related to physical feminization and that this effect may, at least in part, reflect the influence of the hormone estrogen. 相似文献
1000.
Frank H. Guenther Jonathan S. Brumberg E. Joseph Wright Alfonso Nieto-Castanon Jason A. Tourville Mikhail Panko Robert Law Steven A. Siebert Jess L. Bartels Dinal S. Andreasen Princewill Ehirim Hui Mao Philip R. Kennedy 《PloS one》2009,4(12)