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排序方式: 共有6015条查询结果,搜索用时 46 毫秒
961.
962.
Joshua M. Uronis Marcus Mühlbauer Hans H. Herfarth Tara C. Rubinas Gieira S. Jones Christian Jobin 《PloS one》2009,4(6)
It is well established that the intestinal microbiota plays a key role in the pathogenesis of Crohn''s disease (CD) and ulcerative colitis (UC) collectively referred to as inflammatory bowel disease (IBD). Epidemiological studies have provided strong evidence that IBD patients bear increased risk for the development of colorectal cancer (CRC). However, the impact of the microbiota on the development of colitis-associated cancer (CAC) remains largely unknown. In this study, we established a new model of CAC using azoxymethane (AOM)-exposed, conventionalized-Il10−/− mice and have explored the contribution of the host intestinal microbiota and MyD88 signaling to the development of CAC. We show that 8/13 (62%) of AOM-Il10−/− mice developed colon tumors compared to only 3/15 (20%) of AOM- wild-type (WT) mice. Conventionalized AOM-Il10−/− mice developed spontaneous colitis and colorectal carcinomas while AOM-WT mice were colitis-free and developed only rare adenomas. Importantly, tumor multiplicity directly correlated with the presence of colitis. Il10−/− mice mono-associated with the mildly colitogenic bacterium Bacteroides vulgatus displayed significantly reduced colitis and colorectal tumor multiplicity compared to Il10−/− mice. Germ-free AOM-treated Il10−/− mice showed normal colon histology and were devoid of tumors. Il10−/−; Myd88−/− mice treated with AOM displayed reduced expression of Il12p40 and Tnfα mRNA and showed no signs of tumor development. We present the first direct demonstration that manipulation of the intestinal microbiota alters the development of CAC. The TLR/MyD88 pathway is essential for microbiota-induced development of CAC. Unlike findings obtained using the AOM/DSS model, we demonstrate that the severity of chronic colitis directly correlates to colorectal tumor development and that bacterial-induced inflammation drives progression from adenoma to invasive carcinoma. 相似文献
963.
Rodrigo T. Calado Joshua A. Regal David E. Kleiner David S. Schrump Nathan R. Peterson Veronica Pons Stephen J. Chanock Peter M. Lansdorp Neal S. Young 《PloS one》2009,4(11)
Background
Telomerase is an enzyme specialized in maintaining telomere lengths in highly proliferative cells. Loss-of-function mutations cause critical telomere shortening and are associated with the bone marrow failure syndromes dyskeratosis congenita and aplastic anemia and with idiopathic pulmonary fibrosis. Here, we sought to determine the spectrum of clinical manifestations associated with telomerase loss-of-function mutations.Methodology/Principal Findings
Sixty-nine individuals from five unrelated families with a variety of hematologic, hepatic, and autoimmune disorders were screened for telomerase complex gene mutations; leukocyte telomere length was measured by flow fluorescence in situ hybridization in mutation carriers and some non-carriers; the effects of the identified mutations on telomerase activity were determined; and genetic and clinical data were correlated. In six generations of a large family, a loss-of-function mutation in the telomerase enzyme gene TERT associated with severe telomere shortening and a range of hematologic manifestations, from macrocytosis to acute myeloid leukemia, with severe liver diseases marked by fibrosis and inflammation, and one case of idiopathic pulmonary fibrosis but not with autoimmune disorders. Additionally, we identified four unrelated families in which loss-of-function TERC or TERT gene mutations tracked with marrow failure, pulmonary fibrosis, and a spectrum of liver disorders.Conclusions/Significance
These results indicate that heterozygous telomerase loss-of-function mutations associate with but are not determinant of a large spectrum of hematologic and liver abnormalities, with the latter sometimes occurring in the absence of marrow failure. Our findings, along with the link between pulmonary fibrosis and telomerase mutations, also suggest a common pathogenic mechanism for fibrotic diseases in which defective telomere repair plays important role. 相似文献964.
This study tests population genetic patterns across the Eurasian dreissenid mussel invasions of North America—encompassing
the zebra mussel Dreissena polymorpha (1986 detection) and the quagga mussel D. rostriformis
bugensis (detected in 1990, which now has largely displaced the former in the Great Lakes). We evaluate their source-spread relationships
and invasion genetics using 9–11 nuclear microsatellite loci for 583 zebra mussels (21 sites) and 269 quagga mussels (12 sites)
from Eurasian and North American range locations, with the latter including the Great Lakes, Mississippi River basin, Atlantic
coastal waterways, Colorado River system, and California reservoirs. Additionally, mtDNA cytochrome b gene sequences are used to verify species identity. Our results indicate that North American zebra mussels originate from
multiple non-native northern European populations, whereas North American quagga mussels trace to native estuaries in the
Southern Bug and Dnieper Rivers. Invasive populations of both species show considerable genetic diversity and structure (zebra
F
ST = 0.006–0.263, quagga F
ST = 0.008–0.267), without founder effects. Most newer zebra mussel populations have appreciable genetic diversity, whereas
quagga mussel populations from the Colorado River and California show some founder effects. The population genetic composition
of both species changed over time at given sites; with some adding alleles from adjacent populations, some losing them, and
all retaining closest similarity to their original composition. Zebra mussels from Kansas and California appear genetically
similar and assign to a possible origin from the St. Lawrence River, whereas quagga mussels from Nevada and California assign
to a possible origin from Lake Ontario. These assignments suggest that overland colonization pathways via recreational boats
do not necessarily reflect the most proximate connections. In conclusion, our microsatellite results comprise a valuable baseline
for resolving present and future dreissenid mussel invasion pathways. 相似文献
965.
966.
Gerald J. Wilmink Caleb L. Roth Bennett L. Ibey Norma Ketchum Joshua Bernhard Cesario Z. Cerna William P. Roach 《Cell stress & chaperones》2010,15(6):1027-1038
MicroRNAs (miRNAs) are a class of small RNAs that play a critical role in the coordination of fundamental cellular processes.
Recent studies suggest that miRNAs participate in the cellular stress response (CSR), but their specific involvement remains
unclear. In this study, we identify a group of thermally regulated miRNAs (TRMs) that are associated with the CSR. Using miRNA
microarrays, we show that dermal fibroblasts differentially express 123 miRNAs when exposed to hyperthermia. Interestingly,
only 27 of these miRNAs are annotated in the current Sanger registry. We validated the expression of the annotated miRNAs
using qPCR techniques, and we found that the qPCR and microarray data was in well agreement. Computational target-prediction
studies revealed that putative targets for the TRMs are heat shock proteins and Argonaute-2—the core functional unit of RNA
silencing. These results indicate that cells express a specific group of miRNAs when exposed to hyperthermia, and these miRNAs
may function in the regulation of the CSR. Future studies will be conducted to determine if other cells lines differentially
express these miRNAs when exposed to hyperthermia. 相似文献
967.
Defining auxin response contexts in plant development 总被引:1,自引:0,他引:1
968.
Comparisons of genetic variation between humans and great apes are hampered by the fact that we still know little about the demographics and evolutionary history of the latter species. In addition, characterizing ape genetic variation is important because they are threatened with extinction, and knowledge about genetic differentiation among groups may guide conservation efforts. We sequenced multiple intergenic autosomal regions totaling 22,400 base pairs (bp) in ten individuals each from western, central, and eastern chimpanzee groups and in nine bonobos, and 16,000 bp in ten Bornean and six Sumatran orangutans. These regions are analyzed together with homologous information from three human populations and gorillas. We find that whereas orangutans have the highest diversity, western chimpanzees have the lowest, and that the demographic histories of most groups differ drastically. Special attention should therefore be paid to sampling strategies and the statistics chosen when comparing levels of variation within and among groups. Finally, we find that the extent of genetic differentiation among "subspecies" of chimpanzees and orangutans is comparable to that seen among human populations, calling the validity of the "subspecies" concept in apes into question. 相似文献
969.
970.