全文获取类型
收费全文 | 6718篇 |
免费 | 518篇 |
专业分类
7236篇 |
出版年
2024年 | 8篇 |
2023年 | 56篇 |
2022年 | 106篇 |
2021年 | 204篇 |
2020年 | 108篇 |
2019年 | 137篇 |
2018年 | 185篇 |
2017年 | 187篇 |
2016年 | 228篇 |
2015年 | 396篇 |
2014年 | 398篇 |
2013年 | 528篇 |
2012年 | 649篇 |
2011年 | 563篇 |
2010年 | 350篇 |
2009年 | 298篇 |
2008年 | 381篇 |
2007年 | 377篇 |
2006年 | 313篇 |
2005年 | 294篇 |
2004年 | 269篇 |
2003年 | 249篇 |
2002年 | 236篇 |
2001年 | 53篇 |
2000年 | 33篇 |
1999年 | 47篇 |
1998年 | 70篇 |
1997年 | 43篇 |
1996年 | 44篇 |
1995年 | 37篇 |
1994年 | 24篇 |
1993年 | 19篇 |
1992年 | 18篇 |
1991年 | 16篇 |
1990年 | 48篇 |
1989年 | 11篇 |
1988年 | 13篇 |
1987年 | 15篇 |
1986年 | 14篇 |
1985年 | 14篇 |
1984年 | 24篇 |
1983年 | 20篇 |
1982年 | 14篇 |
1981年 | 21篇 |
1980年 | 7篇 |
1979年 | 11篇 |
1978年 | 10篇 |
1975年 | 11篇 |
1974年 | 9篇 |
1973年 | 6篇 |
排序方式: 共有7236条查询结果,搜索用时 0 毫秒
91.
Fuster A Picó C Sánchez J Oliver P Zingaretti MC Murano I Morroni M Hoeller U Goralczyk R Cinti S Palou A 《The Journal of nutritional biochemistry》2008,19(5):295-304
Epidemiological studies have demonstrated that people who eat more fruits and vegetables (rich in carotenoids) and people who have higher serum beta-carotene (BC) levels have a lower risk of cancer, particularly lung cancer. However, the two main human intervention studies of BC supplementation (the ATBC and the CARET trials) revealed an increased risk of lung cancer among smokers and asbestos workers. Previous studies carried out in the ferret have reported that BC effects are related to dose. Here, we treated ferrets with two concentrations of oral BC (0.8 and 3.2 mg/kg body weight per day) for 6 months, using BC in a formulation also containing dl-alpha-tocopherol and ascorbyl palmitate. The effect of the smoke-derived carcinogenic agent benzo[a]pyrene (BP), with or without low-dose BC, was also analysed. We determined the protein levels and mRNA expression levels of activator protein 1 (c-Jun and c-Fos), c-Myc, cyclin D1, proliferating cellular nuclear antigen and retinoic acid receptor beta. We did not find higher levels of cell proliferation markers in the lung of ferrets treated with BC or signals of squamous metaplasia lesions either. On the other hand, although no evident signals of pulmonary carcinogenesis were observed in animals exposed to BP, BC supplementation in these animals may prevent against excess cell proliferation, since this reestablishes Jun protein and cyclin D1 mRNA levels in the lung of BP-exposed animals. In summary, these results show that the combination of BC with alpha-tocopherol and ascorbyl palmitate does not induce pro-oxidant effects in the lung of ferrets. 相似文献
92.
Sergio Luiz Montego Ferreira Junior Elis Regina Dalla Costa Paula Gon?alves dos Santos Harrison Magdinier Gomes Marcia Susana Nunes Silva Leonardo Souza Esteves Martha Maria Oliveira Raquel de Abreu Maschmann Afranio Lineu Kritski Philip Noel Suffys Maria Lucia Rosa Rossetti 《Memórias do Instituto Oswaldo Cruz》2014,109(3):307-314
Drug-resistant tuberculosis (TB) threatens global TB control and is a major public
health concern in several countries. We therefore developed a multiplex assay
(LINE-TB/MDR) that is able to identify the most frequent mutations related to
rifampicin (RMP) and isoniazid (INH) resistance. The assay is based on multiplex
polymerase chain reaction, membrane hybridisation and colorimetric detection
targeting of rpoB and katG genes, as well as the
inhA promoter, which are all known to carry specific mutations
associated with multidrug-resistant TB (MDR-TB). The assay was validated on a
reference panel of 108 M. tuberculosis isolates that were characterised by the
proportion method and by DNA sequencing of the targets. When comparing the
performance of LINE-TB/MDR with DNA sequencing, the sensitivity, specificity and
agreement were 100%, 100% and 100%, respectively, for RMP and 77.6%, 90.6% and 88.9%,
respectively, for INH. Using drug sensibility testing as a reference standard, the
performance of LINE-TB/MDR regarding sensitivity, specificity and agreement was 100%,
100% and 100% (95%), respectively, for RMP and 77%, 100% and 88.7% (82.2-95.1),
respectively, for INH. LINE-TB/MDR was compared with GenoType MTBDRplus for 65
isolates, resulting in an agreement of 93.6% (86.7-97.5) for RIF and 87.4%
(84.3-96.2) for INH. LINE-TB/MDR warrants further clinical validation and may be an
affordable alternative for MDR-TB diagnosis. 相似文献
93.
94.
Structural Organization of Virulence-Associated Plasmids of Yersinia pestis 总被引:6,自引:0,他引:6 下载免费PDF全文
Ping Hu Jeffrey Elliott Paula McCready Evan Skowronski Jeffrey Garnes Arthur Kobayashi Robert R. Brubaker Emilio Garcia 《Journal of bacteriology》1998,180(19):5192-5202
The complete nucleotide sequence and gene organization of the three virulence plasmids from Yersinia pestis KIM5 were determined. Plasmid pPCP1 (9,610 bp) has a GC content of 45.3% and encodes two previously known virulence factors, an associated protein, and a single copy of IS100. Plasmid pCD1 (70,504 bp) has a GC content of 44.8%. It is known to encode a number of essential virulence determinants, regulatory functions, and a multiprotein secretory system comprising the low-calcium response stimulation that is shared with the other two Yersinia species pathogenic for humans (Y. pseudotuberculosis and Y. enterocolitica). A new pseudogene, which occurs as an intact gene in the Y. enterocolitica and Y. pseudotuberculosis-derived analogues, was found in pCD1. It corresponds to that encoding the lipoprotein YlpA. Several intact and partial insertion sequences and/or transposons were also found in pCD1, as well as six putative structural genes with high homology to proteins of unknown function in other yersiniae. The sequences of the genes involved in the replication of pCD1 are highly homologous to those of the cognate plasmids in Y. pseudotuberculosis and Y. enterocolitica, but their localization within the plasmid differs markedly from those of the latter. Plasmid pMT1 (100,984 bp) has a GC content of 50.2%. It possesses two copies of IS100, which are located 25 kb apart and in opposite orientations. Adjacent to one of these IS100 inserts is a partial copy of IS285. A single copy of an IS200-like element (recently named IS1541) was also located in pMT1. In addition to 5 previously described genes, such as murine toxin, capsule antigen, capsule anchoring protein, etc., 30 homologues to genes of several bacterial species were found in this plasmid, and another 44 open reading frames without homology to any known or hypothetical protein in the databases were predicted. 相似文献
95.
Virulence markers associated with Trueperella pyogenes infections in livestock and companion animals 下载免费PDF全文
96.
Luciana da Silva Ruiz Sonia Khouri Rosane Christine Hahn Eriques Gonçalves da Silva Vanessa Krummer Perinazzo de Oliveira Rinaldo Ferreira Gandra Claudete Rodrigues Paula 《Mycopathologia》2013,175(3-4):231-239
Opportunistic infections are an increasingly common problem in hospitals, and the yeast Candida parapsilosis has emerged as an important nosocomial pathogen. The aims of this study were to determine and compare (i) the prevalence rate among C. parapsilosis complex organisms isolated from blood in a public children’s hospital in São Paulo state, (ii) the ability of the complex C. parapsilosis species identified to produce biofilm and (iii) the antifungal susceptibility profiles. Forty-nine (49) specimens of isolated blood yeast were analyzed, previously identified as C. parapsilosis by conventional methods. After the molecular analysis, the isolates were characterized as C. parapsilosis sensu stricto (83.7 %), C. orthopsilosis (10.2 %) and C. metapsilosis (6.1 %). All species were able to form biofilm. The species with the highest biofilm production was C. parapsilosis sensu stricto, followed by C. orthopsilosis and further by C. metapsilosis. All of the strains have demonstrated similar susceptibility to fluconazole, caspofungin, voriconazole, cetoconazole and 5-flucytosine. Only one strain of C. parapsilosis was resistant to amphotericin B. Regarding itraconazole, 66.6 and 43.9 % isolates of C. metapsilosis and C. parapsilosis, respectively, have demonstrated to be susceptible dose-dependent, with one isolate of the latter species resistant to the drug. Candida parapsilosis sensu stricto has demonstrated to be the less susceptible, mainly to amphotericin B, caspofungin and “azoles” such as fluconazole. Therefore, C. metapsilosis and C. orthopsilosis are still involved in a restricted number of infections, but these data have become essential for there are very few studies of these species in Latin America. 相似文献
97.
The effects of lipids on the glycosylation of recombinant human interferon- expressed in a Chinese Hamster Ovary cell line were investigated in batch culture. Lipids form an essential part of the N-glycosylation pathway, and have been shown to improve cell viability. In control (serum-free) medium the proportion of fully-glycosylated interferon- deteriorated reproducibly with time in batch culture, but the lipoprotein supplement ExCyte was shown to minimise this trend. Partially substituting the bovine serum albumin content of the medium with a fatty-acid free preparation also improved interferon- glycosylation, possibly indicating that oxidised lipids carried on Cohn fraction V albumin may damage the glycosylation process.Abbreviations BSA
bovine serum albumin
- CHO
chinese hamster ovary
- DHFR
dihydrofolate reductase
- FCS
foetal calf serum
- IFN-
human interferon-gamma
-
q
IFN
specific interferon production rate
-
specific growth rate
- 2N
doubly-gycosylated
- 1N
singly-glycosylated
- ON
non-glycosylated 相似文献
98.
Edwin W. Taylor Nini Skovgaard Cleo A.C. Leite Marina Sartori Gabrielle S. de Paula Augusto S. Abe 《Journal of thermal biology》2012
Bullfrogs, Lithobathes catesbeianus, bearing a femoral artery cannula were held at 3 temperatures (10, 20 and 30 °C) for 24 h. Changes in heart rate were recorded before and after injection of cholinergic and adrenergic antagonists. Normal heart rate doubled for each temperature increment. Adrenergic tone on the heart varied around 20% at all 3 temperatures but cholinergic tone increased from −5% to 10% between 10 and 30 °C. In contrast, cholinergic tone increased from 75% at 5 °C to 329% at 25 °C in Xenopus laevis. Injection of the neural tracer True Blue into the cervical vagus of the bullfrog revealed a single location for vagal preganglionic neurons (VPN) in the dorsal vagal motor nucleus (DVN), while Xenopus had 30% of its VPN in a ventro-lateral group outside the DVN. Broader comparative studies have suggested that differences in the extent of vagal tone may relate to the location of VPN in the brainstem and this may be the case in these amphibians. 相似文献
99.
DiDonato RJ Arbuckle E Buker S Sheets J Tobar J Totong R Grisafi P Fink GR Celenza JL 《The Plant journal : for cell and molecular biology》2004,37(3):340-353
Lateral root formation, the primary way plants increase their root mass, displays developmental plasticity in response to environmental changes. The aberrant lateral root formation (alf)4-1 mutation blocks the initiation of lateral roots, thus greatly altering root system architecture. We have positionally cloned the ALF4 gene and have further characterized its phenotype. The encoded ALF4 protein is conserved among plants and has no similarities to proteins from other kingdoms. The gene is present in a single copy in Arabidopsis. Using translational reporters for ALF4 gene expression, we have determined that the ALF4 protein is nuclear localized and that the gene is expressed in most plant tissues; however, ALF4 expression and ALF4's subcellular location are not regulated by auxin. These findings taken together with further genetic and phenotypic characterization of the alf4-1 mutant suggest that ALF4 functions independent from auxin signaling and instead functions in maintaining the pericycle in the mitotically competent state needed for lateral root formation. Our results provide genetic evidence that the pericycle shares properties with meristems and that this tissue plays a central role in creating the developmental plasticity needed for root system development. 相似文献
100.