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141.
Joel G. Ray Michael J. Schull Marcelo L. Urquia John J. You Astrid Guttmann Marian J. Vermeulen 《PLoS medicine》2010,7(9)
Background
The association between fetal exposure to major radiodiagnostic testing in pregnancy—computed tomography (CT) and radionuclide imaging—and the risk of childhood cancer is not established.Methods and Findings
We completed a population-based study of 1.8 million maternal-child pairs in the province of Ontario, from 1991 to 2008. We used Ontario''s universal health care–linked administrative databases to identify all term obstetrical deliveries and newborn records, inpatient and outpatient major radiodiagnostic services, as well as all children with a malignancy after birth. There were 5,590 mothers exposed to major radiodiagnostic testing in pregnancy (3.0 per 1,000) and 1,829,927 mothers not exposed. The rate of radiodiagnostic testing increased from 1.1 to 6.3 per 1,000 pregnancies over the study period; about 73% of tests were CT scans. After a median duration of follow-up of 8.9 years, four childhood cancers arose in the exposed group (1.13 per 10,000 person-years) and 2,539 cancers in the unexposed group (1.56 per 10,000 person-years), a crude hazard ratio of 0.69 (95% confidence interval 0.26–1.82). After adjusting for maternal age, income quintile, urban status, and maternal cancer, as well as infant sex, chromosomal or congenital anomalies, and major radiodiagnostic test exposure after birth, the risk was essentially unchanged (hazard ratio 0.68, 95% confidence interval 0.25–1.80).Conclusions
Although major radiodiagnostic testing is now performed in about 1 in 160 pregnancies in Ontario, the absolute annual risk of childhood malignancy following exposure in utero remains about 1 in 10,000. Since the upper confidence limit of the relative risk of malignancy may be as high as 1.8 times that of an unexposed pregnancy, we cannot exclude the possibility that fetal exposure to CT or radionuclide imaging is carcinogenic. Please see later in the article for the Editors'' Summary 相似文献142.
Hansen L Hare KJ Hartmann B Deacon CF Ugleholdt RK Plamboeck A Holst JJ 《Regulatory peptides》2007,138(2-3):126-132
Little is known about the metabolism of the intestinotropic factor glucagon-like peptide-2 (GLP-2); except that it is a substrate for dipeptidyl peptidase IV (DPP-IV) and that it appears to be eliminated by the kidneys. We, therefore, investigated GLP-2 metabolism in six multicatheterized pigs receiving intravenous GLP-2 infusions (2 pmol/kg/min) before and after administration of valine-pyrrolidide (300 mumol/kg; a well characterized DPP-IV inhibitor). Plasma samples were analyzed by radioimmunoassays allowing determination of intact, biologically active GLP-2 and the DPP-IV metabolite GLP-2 (3-33). During infusion of GLP-2 alone, 30.9+/-1.7% of the infused peptide was degraded to GLP-2 (3-33). After valine-pyrrolidide, there was no significant formation of the metabolite. Significant extraction of intact GLP-2 was observed across the kidneys, the extremities (represented by a leg), and the splanchnic bed, resulting in a metabolic clearance rate (MCR) of 6.80+/-0.47 ml/kg/min and a plasma half-life of 6.8+/-0.8 min. Hepatic extraction was not detected. Valine-pyrrolidide addition did not affect extraction ratios significantly, but decreased (p=0.003) MCR to 4.18+/-0.27 ml/kg/min and increased (p=0.052) plasma half-life to 9.9+/-0.8 min. The metabolite was eliminated with a half-life of 22.1+/-2.6 min and a clearance of 2.07+/-0.11 ml/kg/min. In conclusion, intact GLP-2 is eliminated in the peripheral tissues, the splanchnic bed and the kidneys, but not in the liver, by mechanisms unrelated to DPP-IV. However, DPP-IV is involved in the overall GLP-2 metabolism and seems to be the sole enzyme responsible for N-terminal degradation of GLP-2. 相似文献
143.
Species distributions often show an aggregated pattern, which can be due to a number of endo- and exogenous factors. While autologistic models have been used for modelling such data with statistical rigour, little emphasis has been put on disentangling potential causes of aggregation. In this paper we ask whether it is possible to infer sources of aggregation in species distributions from a single set of occurrence data by comparing the performance of various autologistic models. We create simulated data sets, which show similar occupancy patterns, but differ in the process that causes the aggregation. We model the distribution of these data with various autologistic models, and show how the relative performance of the models is sensitive to the factor causing aggregation in the data. This information can be used when modelling real species data, where causes of aggregation are typically unknown. To illustrate, we use our approach to assess the potential causes of aggregation in data of seven bird species with contrasting statistical patterns. Our findings have important implications for conservation, as understanding the mechanisms that drive population fluctuations in space and time is critical for the development of effective management actions for long-term conservation. 相似文献
144.
145.
Tannert A Kurz A Erlemann KR Müller K Herrmann A Schiller J Töpfer-Petersen E Manjunath P Müller P 《European biophysics journal : EBJ》2007,36(4-5):461-475
The bovine seminal plasma protein PDC-109 modulates the maturation of bull sperm cells by removing lipids, mainly phosphatidylcholine
and cholesterol, from their cellular membrane. Here, we have characterized the process of extraction of endogenous phospholipids
and of their respective analogues. By measuring the PDC-109-mediated release of fluorescent phospholipid analogues from lipid
vesicles and from biological membranes (human erythrocytes, bovine epididymal sperm cells), we showed that PDC-109 extracts
phospholipids with a phosphorylcholine headgroup mainly from the outer leaflet of these membranes. The ability of PDC-109
to extract endogenous phospholipids from epididymal sperm cells was followed by mass spectrometry, which allowed us to characterize
the fatty acid pattern of the released lipids. From these cells, PDC-109 extracted phosphatidylcholine and sphingomyelin that
contained an enrichment of mono- and di-unsaturated fatty acids as well as short-chain and lyso-phosphatidylcholine species.
Based on the results, a model explaining the phospholipid specificity of PDC-109-mediated lipid release is presented.
Astrid Tannert and Anke Kurz have contributed equally to this work.
Dedicated to Prof. K. Arnold on the occasion of his 65th birthday. 相似文献
146.
Homozygous mutation in SPATA16 is associated with male infertility in human globozoospermia 总被引:1,自引:0,他引:1 下载免费PDF全文
Dam AH Koscinski I Kremer JA Moutou C Jaeger AS Oudakker AR Tournaye H Charlet N Lagier-Tourenne C van Bokhoven H Viville S 《American journal of human genetics》2007,81(4):813-820
Globozoospermia is a rare (incidence <0.1% in male infertile patients) form of teratozoospermia, mainly characterized by round-headed spermatozoa that lack an acrosome. It originates from a disturbed spermiogenesis, which is expected to be induced by a genetic factor. Several family cases and recessive mouse models with the same phenotype support this expectation. In this study, we present a consanguineous family with three affected brothers, in whom we have identified a homozygous mutation in the spermatogenesis-specific gene SPATA16. This is the first example of a nonsyndromic male infertility condition in humans caused by an autosomal gene defect, and it could also mean that the identification of other partners like SPATA16 could elucidate acrosome formation. 相似文献
147.
Rac is a dominant regulator of cadherin-directed actin assembly that is activated by adhesive ligation independently of Tiam1 总被引:1,自引:0,他引:1
Kraemer A Goodwin M Verma S Yap AS Ali RG 《American journal of physiology. Cell physiology》2007,292(3):C1061-C1069
Classic cadherins function as adhesion-activated cell signaling receptors. On adhesive ligation, cadherins induce signaling cascades leading to actin cytoskeletal reorganization that is imperative for cadherin function. In particular, cadherin ligation activates actin assembly by the actin-related protein (Arp)2/3 complex, a process that critically affects the ability of cells to form and extend cadherin-based contacts. However, the signaling pathway(s) that activate Arp2/3 downstream of cadherin adhesion remain poorly understood. In this report we focused on the Rho family GTPases Rac and Cdc42, which can signal to Arp2/3. We found that homophilic engagement of E-cadherin simultaneously activates both Rac1 and Cdc42. However, by comparing the impact of dominant-negative Rac1 and Cdc42 mutants, we show that Rac1 is the dominant regulator of cadherin-directed actin assembly and homophilic contact formation. To pursue upstream elements of the Rac1 signaling pathway, we focused on the potential contribution of Tiam1 to cadherin-activated Rac signaling. We found that Tiam1 or the closely-related Tiam2/STEF1 was recruited to cell-cell contacts in an E-cadherin-dependent fashion. Moreover, a dominant-negative Tiam1 mutant perturbed cell spreading on cadherin-coated substrata. However, disruption of Tiam1 activity with dominant-negative mutants or RNA interference did not affect the ability of E-cadherin ligation to activate Rac1. We conclude that Rac1 critically influences cadherin-directed actin assembly as part of a signaling pathway independent of Tiam1. actin cytoskeleton; Cdc42; E-cadherin 相似文献
148.
149.
Nathan W. Ayer Peter H. Tyedmers Nathan L. Pelletier Ulf Sonesson Astrid Scholz 《The International Journal of Life Cycle Assessment》2007,12(7):480-487