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51.
Fife MS Gutierrez A Ogilvie EM Stock CJ Samuel JM Thomson W Mack LF Lewis CM Woo P 《Arthritis research & therapy》2006,8(5):R148-5
Juvenile idiopathic arthritis (JIA) is the most common cause of chronic childhood disability and encompasses a number of disease
subgroups. In this study we have focused on systemic JIA (sJIA), which accounts for approximately 11% of UK JIA cases. This
study reports the investigation of three members of the IL10 gene family as candidate susceptibility loci in children with
sJIA. DNA from 473 unaffected controls and 172 patients with sJIA was genotyped for a single nucleotide polymorphism (SNP)
in IL19 and IL20 and two SNPs in IL10. We examined evidence for association of the four SNPs by single marker and haplotype
analysis. Significant differences in allele frequency were observed between cases and controls, for both IL10-1082 (p = 0.031)
and IL20-468 (p = 0.028). Furthermore, examination of the haplotypes of IL10-1082 and IL20-468 revealed greater evidence for
association (global p = 0.0006). This study demonstrates a significant increased prevalence of the low expressing IL10-1082
genotype in patients with sJIA. In addition, we show a separate association with an IL20 polymorphism, and the IL10-1082A/IL20-468T
haplotype. The two marker 'A-T' haplotype confers an odds ratio of 2.24 for sJIA. This positive association suggests an important
role for these cytokines in sJIA pathogenesis. 相似文献
52.
Tyler JW Robinson Melody Pai Jeff C Liu Frederick Vizeacoumar Thomas Sun Sean E Egan Alessandro Datti Jing Huang Eldad Zacksenhaus 《Cell cycle (Georgetown, Tex.)》2013,12(18):3013-3024
Triple-negative breast cancer (TNBC) represents an aggressive subtype, for which radiation and chemotherapy are the only options. Here we describe the identification of disulfiram, an FDA-approved drug used to treat alcoholism, as well as the related compound thiram, as the most potent growth inhibitors following high-throughput screens of 3185 compounds against multiple TNBC cell lines. The average IC50 for disulfiram was ~300 nM. Drug affinity responsive target stability (DARTS) analysis identified IQ motif-containing factors IQGAP1 and MYH9 as direct binding targets of disulfiram. Indeed, knockdown of these factors reduced, though did not completely abolish, cell growth. Combination treatment with 4 different drugs commonly used to treat TNBC revealed that disulfiram synergizes most effectively with doxorubicin to inhibit cell growth of TNBC cells. Disulfiram and doxorubicin cooperated to induce cell death as well as cellular senescence, and targeted the ESA+/CD24-/low/CD44+ cancer stem cell population. Our results suggest that disulfiram may be repurposed to treat TNBC in combination with doxorubicin. 相似文献
53.
CHRISTOPHER J. KATZ SCOTT C. ANDERSON ROBERT W. HOWE ANDREW R. HINICKLE NICOLE T. WALISZEWSKI STACY A. NYE AARON M. WUNDERLIN 《The Journal of wildlife management》2007,71(2):634-636
ABSTRACT Knowledge of the distribution and pathology of West Nile virus (WNV) in black bears is a necessary tool that allows wildlife managers to implement a management plan, set harvest quotas, and relocate nuisance bears. We studied the presence and significance of WNV titers in free-roaming black bears (Ursus americanus) in northeastern Wisconsin between February 2003 and March 2005. Serum neutralizing antibodies to WNV, with confirmation by plaque-reduction neutralization test to both WNV and Saint Louis encephalitis, identified exposure in 13 of 74 (17.6%) bears. This compares with a 6% infection rate in black bears in Virginia and 22% in European brown bears (Ursus arctos). Pathologic effects from exposure to WNV were not seen in any of the black bears studied. 相似文献
54.
Past and present distribution, densities and movements of blue whales Balaenoptera musculus in the Southern Hemisphere and northern Indian Ocean 总被引:3,自引:0,他引:3
T. A. BRANCH K. M. STAFFORD D. M. PALACIOS C. ALLISON J. L. BANNISTER C. L. K. BURTON E. CABRERA C. A. CARLSON B. GALLETTI VERNAZZANI P. C. GILL R. HUCKE‐GAETE K. C. S. JENNER M.‐N. M. JENNER K. MATSUOKA Y. A. MIKHALEV T. MIYASHITA M. G. MORRICE S. NISHIWAKI V. J. STURROCK D. TORMOSOV R. C. ANDERSON A. N. BAKER P. B. BEST P. BORSA R. L. BROWNELL JR S. CHILDERHOUSE K. P. FINDLAY T. GERRODETTE A. D. ILANGAKOON M. JOERGENSEN B. KAHN D. K. LJUNGBLAD B. MAUGHAN R. D. MCCAULEY S. MCKAY T. F. NORRIS S. RANKIN F. SAMARAN D. THIELE K. VAN WAEREBEEK R. M. WARNEKE 《Mammal Review》2007,37(2):116-175
- 1 Blue whale locations in the Southern Hemisphere and northern Indian Ocean were obtained from catches (303 239), sightings (4383 records of ≥8058 whales), strandings (103), Discovery marks (2191) and recoveries (95), and acoustic recordings.
- 2 Sighting surveys included 7 480 450 km of effort plus 14 676 days with unmeasured effort. Groups usually consisted of solitary whales (65.2%) or pairs (24.6%); larger feeding aggregations of unassociated individuals were only rarely observed. Sighting rates (groups per 1000 km from many platform types) varied by four orders of magnitude and were lowest in the waters of Brazil, South Africa, the eastern tropical Pacific, Antarctica and South Georgia; higher in the Subantarctic and Peru; and highest around Indonesia, Sri Lanka, Chile, southern Australia and south of Madagascar.
- 3 Blue whales avoid the oligotrophic central gyres of the Indian, Pacific and Atlantic Oceans, but are more common where phytoplankton densities are high, and where there are dynamic oceanographic processes like upwelling and frontal meandering.
- 4 Compared with historical catches, the Antarctic (‘true’) subspecies is exceedingly rare and usually concentrated closer to the summer pack ice. In summer they are found throughout the Antarctic; in winter they migrate to southern Africa (although recent sightings there are rare) and to other northerly locations (based on acoustics), although some overwinter in the Antarctic.
- 5 Pygmy blue whales are found around the Indian Ocean and from southern Australia to New Zealand. At least four groupings are evident: northern Indian Ocean, from Madagascar to the Subantarctic, Indonesia to western and southern Australia, and from New Zealand northwards to the equator. Sighting rates are typically much higher than for Antarctic blue whales.
- 6 South‐east Pacific blue whales have a discrete distribution and high sighting rates compared with the Antarctic. Further work is needed to clarify their subspecific status given their distinctive genetics, acoustics and length frequencies.
- 7 Antarctic blue whales numbered 1700 (95% Bayesian interval 860–2900) in 1996 (less than 1% of original levels), but are increasing at 7.3% per annum (95% Bayesian interval 1.4–11.6%). The status of other populations in the Southern Hemisphere and northern Indian Ocean is unknown because few abundance estimates are available, but higher recent sighting rates suggest that they are less depleted than Antarctic blue whales.
55.
Kan Chen Wanlu Cao Juan Li Dave Sprengers Pratika Y Hernanda Xiangdong Kong Luc JW van der Laan Kwan Man Jaap Kwekkeboom Herold J Metselaar Maikel P Peppelenbosch Qiuwei Pan 《Molecular medicine (Cambridge, Mass.)》2015,21(1):792-802
As uncontrolled cell proliferation requires nucleotide biosynthesis, inhibiting enzymes that mediate nucleotide biosynthesis constitutes a rational approach to the management of oncological diseases. In practice, however, results of this strategy are mixed and thus elucidation of the mechanisms by which cancer cells evade the effect of nucleotide biosynthesis restriction is urgently needed. Here we explored the notion that intrinsic differences in cancer cell cycle velocity are important in the resistance toward inhibition of inosine monophosphate dehydrogenase (IMPDH) by mycophenolic acid (MPA). In short-term experiments, MPA treatment of fast-growing cancer cells effectively elicited G0/G1 arrest and provoked apoptosis, thus inhibiting cell proliferation and colony formation. Forced expression of a mutated IMPDH2, lacking a binding site for MPA but retaining enzymatic activity, resulted in complete resistance of cancer cells to MPA. In nude mice subcutaneously engrafted with HeLa cells, MPA moderately delayed tumor formation by inhibiting cell proliferation and inducing apoptosis. Importantly, we developed a lentiviral vector–based Tet-on label-retaining system that enables to identify, isolate and functionally characterize slow-cycling or so-called label-retaining cells (LRCs) in vitro and in vivo. We surprisingly found the presence of LRCs in fast-growing tumors. LRCs were superior in colony formation, tumor initiation and resistance to MPA as compared with fast-cycling cells. Thus, the slow-cycling compartment of cancer seems predominantly responsible for resistance to MPA. 相似文献
56.
ANDREW V. BRADLEY FRANCE F. GERARD NICOLAS BARBIER GRAHAM P. WEEDON LIANA O. ANDERSON CHRIS HUNTINGFORD LUIZ E. O. C. ARAGÃO PRZEMYSLAW ZELAZOWSKI EGIDIO ARAI 《Global Change Biology》2011,17(6):2245-2260
In tropical areas, Dynamic Global Vegetation Models (DGVMs) still have deficiencies in simulating the timing of vegetation phenology. To start addressing this problem, standard Fourier‐based methods are applied to aerosol screened monthly remotely sensed phenology time series (Enhanced Vegetation Index, EVI) and two major driving factors of phenology: solar radiation and precipitation (for March 2000 through December 2006 over northern South America). At 1 × 1 km scale using, power (or variance) spectra on good quality aerosol screened time series, annual cycles in EVI are detected across 58.24% of the study area, the strongest (largest amplitude) occurring in the savanna. Terra Firme forest have weak but significant annual cycles in comparison with savannas because of the heterogeneity of vegetation and nonsynchronous phenological events within 1 × 1 km scale pixels. Significant annual cycles for radiation and precipitation account for 86% and 90% of the region, respectively, with different spatial patterns to phenology. Cross‐spectral analysis was used to compare separately radiation with phenology/EVI, precipitation with phenology/EVI and radiation with precipitation. Overall the majority of the Terra Firme forest appears to have radiation as the driver of phenology (either radiation is in phase or leading phenology/EVI at the annual scale). These results are in agreement with previous research, although in Acre, central and eastern Peru and northern Bolivia there is a coexistence of ‘in phase’ precipitation over Terra Firme forest. In contrast in most areas of savanna precipitation appears to be a driver and savanna areas experiencing an inverse (antiphase) relationship between radiation and phenology is consistent with inhibited grassland growth due to soil moisture limitation. The resulting maps provide a better spatial understanding of phenology–driver relationships offering a bench mark to parameterize ecological models. 相似文献
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