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21.
Methods for surveillance of fetal alcohol syndrome: The fetal alcohol syndrome surveillance network II (FASSNetII) – Arizona,Colorado, New York, 2009 ‐ 2014
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Leslie A. O'Leary Linnette Ortiz April Montgomery Deborah J. Fox Christopher Cunniff Margaret Ruttenber April Breen Sydney Pettygrove Don Klumb Charlotte Druschel Jaime L. Frías Luther K. Robinson Jacquelyn Bertrand Kelly Ferrara Maureen Kelly Suzanne M. Gilboa F. John Meaney for the FASSNetII 《Birth defects research. Part A, Clinical and molecular teratology》2015,103(3):196-202
22.
Jennifer B. Nagashima Skylar R. Sylvester Jacquelyn L. Nelson Soon Hon Cheong Chinatsu Mukai Colleen Lambo James A. Flanders Vicki N. Meyers-Wallen Nucharin Songsasen Alexander J. Travis 《PloS one》2015,10(12)
Development of assisted reproductive technologies (ART) in the dog has resisted progress for decades, due to their unique reproductive physiology. This lack of progress is remarkable given the critical role ART could play in conserving endangered canid species or eradicating heritable disease through gene-editing technologies—an approach that would also advance the dog as a biomedical model. Over 350 heritable disorders/traits in dogs are homologous with human conditions, almost twice the number of any other species. Here we report the first live births from in vitro fertilized embryos in the dog. Adding to the practical significance, these embryos had also been cryopreserved. Changes in handling of both gametes enabled this progress. The medium previously used to capacitate sperm excluded magnesium because it delayed spontaneous acrosome exocytosis. We found that magnesium significantly enhanced sperm hyperactivation and ability to undergo physiologically-induced acrosome exocytosis, two functions essential to fertilize an egg. Unlike other mammals, dogs ovulate a primary oocyte, which reaches metaphase II on Days 4–5 after the luteinizing hormone (LH) surge. We found that only on Day 6 are oocytes consistently able to be fertilized. In vitro fertilization of Day 6 oocytes with sperm capacitated in medium supplemented with magnesium resulted in high rates of embryo development (78.8%, n = 146). Intra-oviductal transfer of nineteen cryopreserved, in vitro fertilization (IVF)-derived embryos resulted in seven live, healthy puppies. Development of IVF enables modern genetic approaches to be applied more efficiently in dogs, and for gamete rescue to conserve endangered canid species. 相似文献
23.
Inhibition of nitric oxide synthase enhances contractile response of ventricular myocytes from streptozotocin-diabetic rats 总被引:1,自引:0,他引:1
The contractile hyporesponsiveness of the streptozotocin diabetic rat heart in vitro to β-adrenergic agonists is eliminated
when the heart is perfused with NG-nitro-l-arginine methyl ester (l-NAME), a non-selective inhibitor of nitric oxide synthase (NOS). The following study evaluated the hypothesis that an increased
production of NO/cGMP within the diabetic myocyte inhibits the β-adrenergic-stimulated increase in calcium current and contractile
response. Male Sprague-Dawley rats were given an intravenous injection of streptozotocin (60 mg/kg). After 8 weeks, L-type
calcium currents were recorded in ventricular myocytes using the whole cell voltage-clamp method. Shortening of isolated myocytes
was determined using a video edge detection system. cAMP and cGMP were measured using radioimmunoassay. Nitric oxide production
was determined using the Griess assay kit. Basal cGMP levels and nitric oxide production were elevated in diabetic myocytes.
Shortening of the diabetic myocytes in response to isoproterenol (1 μM) was markedly diminished. However, there was no detectable
difference in the isoproterenol-stimulated L-type calcium current or cAMP levels between control and diabetic myocytes. Acute
superfusion of the diabetic myocyte with l-NAME (1 mM) decreased basal cGMP and markedly enhanced the shortening response to isoproterenol but did not alter isoproterenol-stimulated
calcium current. These data suggest that increased production of NO/cGMP within the diabetic myocyte suppressed β-adrenergic
stimulated shortening of the myocyte. However, NO/cGMP apparently does not suppress shortening of the myocyte by inhibition
of the β-stimulated calcium current. 相似文献
24.
Comparison of topological clustering within protein networks using edge metrics that evaluate full sequence,full structure,and active site microenvironment similarity
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Janelle B Leuthaeuser Stacy T Knutson Kiran Kumar Patricia C Babbitt Jacquelyn S Fetrow 《Protein science : a publication of the Protein Society》2015,24(9):1423-1439
The development of accurate protein function annotation methods has emerged as a major unsolved biological problem. Protein similarity networks, one approach to function annotation via annotation transfer, group proteins into similarity-based clusters. An underlying assumption is that the edge metric used to identify such clusters correlates with functional information. In this contribution, this assumption is evaluated by observing topologies in similarity networks using three different edge metrics: sequence (BLAST), structure (TM-Align), and active site similarity (active site profiling, implemented in DASP). Network topologies for four well-studied protein superfamilies (enolase, peroxiredoxin (Prx), glutathione transferase (GST), and crotonase) were compared with curated functional hierarchies and structure. As expected, network topology differs, depending on edge metric; comparison of topologies provides valuable information on structure/function relationships. Subnetworks based on active site similarity correlate with known functional hierarchies at a single edge threshold more often than sequence- or structure-based networks. Sequence- and structure-based networks are useful for identifying sequence and domain similarities and differences; therefore, it is important to consider the clustering goal before deciding appropriate edge metric. Further, conserved active site residues identified in enolase and GST active site subnetworks correspond with published functionally important residues. Extension of this analysis yields predictions of functionally determinant residues for GST subgroups. These results support the hypothesis that active site similarity-based networks reveal clusters that share functional details and lay the foundation for capturing functionally relevant hierarchies using an approach that is both automatable and can deliver greater precision in function annotation than current similarity-based methods. 相似文献
25.
26.
Male euglossine bees were sampled with chemical baits every two months from September 1997 to July 1999 at nine sites in the Desengano mountain range, Rio de Janeiro State, Brazil. Four sites were located in Atlantic Forest mature second growth, two sites in disturbed forest, and three sites in forest fragments of 200, 156, and 14 ha, respectively. We collected 3653 male euglossine bees from at least 21 species. Analyses of variance indicated no differences among the three habitat types for total number of bees, and 5 of the 6 dominant species. Bootstrapping indicated significant variation in species richness and diversity for some sites, but there was no clear indication of differences among habitats. Similarity as measured with the Morisita–Horn index was inversely related to distance between sites, but relatively high for most site combinations. These results suggest that the euglossine bee community in the three habitats was essentially the same. Although some species were associated with each habitat type, most appeared to respond to temporal local conditions. Our results do not support the hypothesis that forest fragmentation or habitat alteration reduces abundance and diversity of euglossine bees. 相似文献
27.
28.
Larkin J Renukaradhya GJ Sriram V Du W Gervay-Hague J Brutkiewicz RR 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(1):268-279
NK T (NKT) cells are an important component of the innate immune system and recognize the MHC class I-like CD1d molecule. NKT cells possess significant immunoregulatory activity due to their rapid secretion of large quantities of pro- and anti-inflammatory cytokines following CD1d-dependent stimulation. Because the innate immune system is programmed to respond to a multitude of diverse stimuli and must be able to quickly differentiate between pathogenic and endogenous signals, we hypothesized that, apart from stimulation via the TCR (e.g., CD1d-dependent activation), there must be multiple activation pathways that can be triggered through other cell surface receptors on NKT cells. Therefore, we analyzed the ability of CD44, a structurally diverse cell surface receptor expressed on most cells, to stimulate murine NKT cells, compared with conventional T cells. Stimulation of CD44 through Ab cross-linking or binding to its natural ligands hyaluronan and osteopontin induced NKT cells to secrete cytokines, up-regulate activation markers, undergo morphological changes, and resist activation-induced cell death, whereas conventional T cells only exhibited changes in morphology and protection from activation-induced cell death. This CD44-specific stimulation of NKT cells correlated with their ability to bind hyaluronan. Thus, fundamental differences in CD44 function between these lymphocyte subsets suggest an important biological role for CD44 in the innate immune response. 相似文献
29.
Choi BS Sondel PM Hank JA Schalch H Gan J King DM Kendra K Mahvi D Lee LY Kim K Albertini MR 《Cancer immunology, immunotherapy : CII》2006,55(7):761-774
Purpose: We conducted a phase I trial of interleukin 2 (IL-2) in combination with chimeric 14.18 (ch14.18) and murine R24 antibodies
to determine the maximal tolerated dose (MTD), immunological effects, and toxicity of this treatment combination. Experimental Design: Twenty-seven patients with either melanoma (23 patients) or sarcoma (4 patients) were enrolled to receive a combination
therapy with ch14.18 and R24 antibodies together with continuous infusion of Roche IL-2 (1.5×106 U/m2/day, 26 patients) or Chiron IL-2 (4.5×106 U/m2/day, 1 patient) given 4 days/week for 3 weeks. The antibodies ch14.18 (2–7.5 mg/m2/day) and R24 (1–10 mg/m2/day) were scheduled to be administered for 5 days during the second week of IL-2 therapy. Results: When given in combination in this study, the MTD for ch14.18 was 5 mg/m2/day and the MTD for R24 was 5 mg/m2/day. Dose-limiting toxicities were severe allergic reactions to both ch14.18 and R24 as well as pain related to ch14.18.
This ch14.18 MTD was lower than the 7.5 mg/m2/day MTD previously determined for ch14.18 given alone with the same dose and schedule of IL-2. Immunological effects included
the induction of lymphokine-activated killer (LAK) activity and antibody-dependent cell-mediated cytoxicity (ADCC). Anti-idiotype
response to ch14.18 was seen in six patients, including two melanoma patients who had a partial response to treatment. In
addition to two partial responses, four patients had a stable disease and one patient remained without any evidence of disease.
Conclusions: Immunotherapy with IL-2 in combination with ch14.18 and R24 antibodies augments LAK function and ADCC measured in vitro
in all patients. While there exist theoretical advantages of combining these two antibodies, the MTD of ch14.18 and of R24
were lower than the MTD of each antibody in prior studies evaluating single antibody therapy with IL-2. As such, the combination
of these two antibodies together with IL-2 therapy appeared to influence the MTD and toxicity of each of the administered
antibodies.
This work is supported by NIH grants M01-RR03186, R01-CA32685, and P30-CA14520 相似文献
30.
VEGF modulates erythropoiesis through regulation of adult hepatic erythropoietin synthesis 总被引:4,自引:0,他引:4
Tam BY Wei K Rudge JS Hoffman J Holash J Park SK Yuan J Hefner C Chartier C Lee JS Jiang S Nayak NR Niyak NR Kuypers FA Ma L Sundram U Wu G Garcia JA Schrier SL Maher JJ Johnson RS Yancopoulos GD Mulligan RC Kuo CJ 《Nature medicine》2006,12(7):793-800
Vascular endothelial growth factor (VEGF) exerts crucial functions during pathological angiogenesis and normal physiology. We observed increased hematocrit (60-75%) after high-grade inhibition of VEGF by diverse methods, including adenoviral expression of soluble VEGF receptor (VEGFR) ectodomains, recombinant VEGF Trap protein and the VEGFR2-selective antibody DC101. Increased production of red blood cells (erythrocytosis) occurred in both mouse and primate models, and was associated with near-complete neutralization of VEGF corneal micropocket angiogenesis. High-grade inhibition of VEGF induced hepatic synthesis of erythropoietin (Epo, encoded by Epo) >40-fold through a HIF-1alpha-independent mechanism, in parallel with suppression of renal Epo mRNA. Studies using hepatocyte-specific deletion of the Vegfa gene and hepatocyte-endothelial cell cocultures indicated that blockade of VEGF induced hepatic Epo by interfering with homeostatic VEGFR2-dependent paracrine signaling involving interactions between hepatocytes and endothelial cells. These data indicate that VEGF is a previously unsuspected negative regulator of hepatic Epo synthesis and erythropoiesis and suggest that levels of Epo and erythrocytosis could represent noninvasive surrogate markers for stringent blockade of VEGF in vivo. 相似文献