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111.
Richard S. Legro Karl R. Hansen Michael P. Diamond Anne Z. Steiner Christos Coutifaris Marcelle I. Cedars Kathleen M. Hoeger Rebecca Usadi Erica B. Johnstone Daniel J. Haisenleder Robert A. Wild Kurt T. Barnhart Jennifer Mersereau J. C. Trussell Stephen A. Krawetz Penny M. Kris-Etherton David B. Sarwer Nanette Santoro Esther Eisenberg Hao Huang Heping Zhang for the Reproductive Medicine Network 《PLoS medicine》2022,19(1)
BackgroundWomen with obesity and infertility are counseled to lose weight prior to conception and infertility treatment to improve pregnancy rates and birth outcomes, although confirmatory evidence from randomized trials is lacking. We assessed whether a preconception intensive lifestyle intervention with acute weight loss is superior to a weight neutral intervention at achieving a healthy live birth.Methods and findingsIn this open-label, randomized controlled study (FIT-PLESE), 379 women with obesity (BMI ≥ 30 kg/m2) and unexplained infertility were randomly assigned in a 1:1 ratio to 2 preconception lifestyle modification groups lasting 16 weeks, between July 2015 and July 2018 (final follow-up September 2019) followed by infertility therapy. The primary outcome was the healthy live birth (term infant of normal weight without major anomalies) incidence. This was conducted at 9 academic health centers across the United States. The intensive group underwent increased physical activity and weight loss (target 7%) through meal replacements and medication (Orlistat) compared to a standard group with increased physical activity alone without weight loss. This was followed by standardized empiric infertility treatment consisting of 3 cycles of ovarian stimulation/intrauterine insemination. Outcomes of any resulting pregnancy were tracked. Among 191 women randomized to standard lifestyle group, 40 dropped out of the study before conception; among 188 women randomized to intensive lifestyle group, 31 dropped out of the study before conception. All the randomized women were included in the intent-to-treat analysis for primary outcome of a healthy live birth. There were no significant differences in the incidence of healthy live births [standard 29/191(15.2%), intensive 23/188(12.2%), rate ratio 0.81 (0.48 to 1.34), P = 0.40]. Intensive had significant weight loss compared to standard (−6.6 ± 5.4% versus −0.3 ± 3.2%, P < 0.001). There were improvements in metabolic health, including a marked decrease in incidence of the metabolic syndrome (baseline to 16 weeks: standard: 53.6% to 49.4%, intensive 52.8% to 32.2%, P = 0.003). Gastrointestinal side effects were significantly more common in intensive. There was a higher, but nonsignificant, first trimester pregnancy loss in the intensive group (33.3% versus 23.7% in standard, 95% rate ratio 1.40, 95% confidence interval [CI]: 0.79 to 2.50). The main limitations of the study are the limited power of the study to detect rare complications and the design difficulty in finding an adequate time matched control intervention, as the standard exercise intervention may have potentially been helpful or harmful.ConclusionsA preconception intensive lifestyle intervention for weight loss did not improve fertility or birth outcomes compared to an exercise intervention without targeted weight loss. Improvement in metabolic health may not translate into improved female fecundity.Trial registrationClinicalTrials.gov .Richard Legro and colleagues investigate the impact of a preconception weight loss intervention on healthy live birth rates in women with obesity and unexplained infertility. NCT02432209相似文献
112.
Ritabrata Dutta Karim Zouaoui Boudjeltia Christos Kotsalos Alexandre Rousseau Daniel Ribeiro de Sousa Jean-Marc Desmet Alain Van Meerhaeghe Antonietta Mira Bastien Chopard 《PLoS computational biology》2022,18(3)
Cardio/cerebrovascular diseases (CVD) have become one of the major health issue in our societies. But recent studies show that the present pathology tests to detect CVD are ineffectual as they do not consider different stages of platelet activation or the molecular dynamics involved in platelet interactions and are incapable to consider inter-individual variability. Here we propose a stochastic platelet deposition model and an inferential scheme to estimate the biologically meaningful model parameters using approximate Bayesian computation with a summary statistic that maximally discriminates between different types of patients. Inferred parameters from data collected on healthy volunteers and different patient types help us to identify specific biological parameters and hence biological reasoning behind the dysfunction for each type of patients. This work opens up an unprecedented opportunity of personalized pathology test for CVD detection and medical treatment. 相似文献
113.
Crystal structures and enzymatic properties of three formyltransferases from archaea: environmental adaptation and evolutionary relationship 下载免费PDF全文
Mamat B Roth A Grimm C Ermler U Tziatzios C Schubert D Thauer RK Shima S 《Protein science : a publication of the Protein Society》2002,11(9):2168-2178
Formyltransferase catalyzes the reversible formation of formylmethanofuran from N(5)-formyltetrahydromethanopterin and methanofuran, a reaction involved in the C1 metabolism of methanogenic and sulfate-reducing archaea. The crystal structure of the homotetrameric enzyme from Methanopyrus kandleri (growth temperature optimum 98 degrees C) has recently been solved at 1.65 A resolution. We report here the crystal structures of the formyltransferase from Methanosarcina barkeri (growth temperature optimum 37 degrees C) and from Archaeoglobus fulgidus (growth temperature optimum 83 degrees C) at 1.9 A and 2.0 A resolution, respectively. Comparison of the structures of the three enzymes revealed very similar folds. The most striking difference found was the negative surface charge, which was -32 for the M. kandleri enzyme, only -8 for the M. barkeri enzyme, and -11 for the A. fulgidus enzyme. The hydrophobic surface fraction was 50% for the M. kandleri enzyme, 56% for the M. barkeri enzyme, and 57% for the A. fulgidus enzyme. These differences most likely reflect the adaptation of the enzyme to different cytoplasmic concentrations of potassium cyclic 2,3-diphosphoglycerate, which are very high in M. kandleri (>1 M) and relatively low in M. barkeri and A. fulgidus. Formyltransferase is in a monomer/dimer/tetramer equilibrium that is dependent on the salt concentration. Only the dimers and tetramers are active, and only the tetramers are thermostable. The enzyme from M. kandleri is a tetramer, which is active and thermostable only at high concentrations of potassium phosphate (>1 M) or potassium cyclic 2,3-diphosphoglycerate. Conversely, the enzyme from M. barkeri and A. fulgidus already showed these properties, activity and stability, at much lower concentrations of these strong salting-out salts. 相似文献
114.
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116.
Kunesová G Hlavácek J Patocka J Evangelou A Zikos C Benaki D Paravatou-Petsotas M Pelecanou M Livaniou E Slaninova J 《Peptides》2008,29(11):1982-1987
Humanin (HN) and its analogues have been shown to protect cells against death induced by various Alzheimer's disease (AD) genes and amyloid-beta-peptides in vitro; the analogues [Gly(14)]-HN and colivelin have also been shown to be potent in reversing learning and memory impairment induced by scopolamine or quinuclidinyl benzilate (QNB) in mice or rats in vivo using the Y-maze or multiple T-maze tests. This paper describes the activity of new peptides of the HN family, after i.p. administration, on QNB-induced impairment of spatial memory in the multiple T-maze test in rats. The following peptides have been studied: HN analogues truncated either on the C- or N-terminus, or analogues having a tert-Leu in place of Leu in the central part of the molecule, the active HN core PAGASRLLLLTGEIDLP (RG-PAGA) and its analogues having three or five leucines instead of four, and finally the recently described hybrid peptide colivelin (i.e. a peptide having the activity-dependent neurotrophic factor SALLRSIPA attached to the N-terminus of the active RG-PAGA) and its des-Leu- and plus-Leu-analogues. While the truncated analogues and most of the tert-Leu containing analogues were devoid of activity, the analogues of the RG-PAGA were active, i.e. they reversed the impairment of spatial memory irrespective of the number of Leu present in their sequence. The highest activity was shown by colivelin and its des-Leu-analogue. These results demonstrate the potential of HN analogues in the modulation of the cholinergic system, which plays an important role in the cognitive deficits associated with AD and other neurodegenerative diseases. 相似文献
117.
Lucia Bertuccini Christine C. Wirth Natalie C. Silmon de Monerri Lefteris Spanos Michael J. Blackman Christos Louis Gabriele Pradel Inga Siden‐Kiamos 《Cellular microbiology》2013,15(8):1438-1455
Successful gametogenesis of the malaria parasite depends on egress of the gametocytes from the erythrocytes within which they developed. Egress entails rupture of both the parasitophorous vacuole membrane and the erythrocyte plasma membrane, and precedes the formation of the motile flagellated male gametes in a process called exflagellation. We show here that egress of the male gametocyte depends on the function of a perforin‐like protein, PPLP2. A mutant of Plasmodium berghei lacking PPLP2 displayed abnormal exflagellation; instead of each male gametocyte forming eight flagellated gametes, it produced gametocytes with only one, shared thicker flagellum. Using immunofluorescence and transmission electron microscopy analysis, and phenotype rescue with saponin or a pore‐forming toxin, we conclude that rupture of the erythrocyte membraneis blocked in the mutant. The parasitophorous vacuole membrane, on the other hand, is ruptured normally. Some mutant parasites are still able to develop in the mosquito, possibly because the vigorous motility of the flagellated gametes eventually leads to escape from the persisting erythrocyte membrane. This is the first example of a perforin‐like protein in Plasmodium parasites having a role in egress from the host cell and the first parasite protein shown to be specifically required for erythrocyte membrane disruption during egress. 相似文献
118.
Konstantinos Dafopoulos Christos Venetis Christina I Messini Spyros Pournaras George Anifandis Antonios Garas Ioannis E Messinis 《Reproductive biology and endocrinology : RB&E》2011,9(1):59
Objectives
It has been suggested that inhibin secretion is altered in women with the polycystic ovary syndrome (PCOS). However, the contribution of a preceding luteal phase has not been taken into account. The aim of the present study was to investigate whether progesterone in the context of a simulated luteal phase affects basal and FSH-induced inhibin secretion in women with PCOS and elevated LH. 相似文献119.
Christos Arvanitidis Georgios Chatzigeorgiou Drosos Koutsoubas Theodoros Kevrekidis Costas Dounas Anastasios Eleftheriou Panayota Koulouri Athanasios Mogias 《Helgoland Marine Research》2005,59(3):177-186
An attempt is made to compare the results of different rapid biodiversity assessment techniques at the pan-Mediterranean, sectorial and local levels. A uniform multivariate pattern exists at the pan-Mediterranean and national (sectorial) levels: lagoons can be different when they host only a few species, but as species numbers increase, lagoons become homogenous in composition. Multivariate techniques cannot distinguish anthropogenically-impacted lagoons from those, which are naturally disturbed. In the pan-Mediterranean context it is the higher taxonomic levels, but in the national and local context it is the most abundant macrobenthic groups (polychaetes, molluscs and crustaceans) and meiobenthos which provide patterns closest to that derived from the species level. Taxonomic distinctness indices applied to polychaete and mollusc inventories provide meaningful results at most levels and scales of observation. These indices seem to be robust enough to discriminate anthropogenically impacted from naturally disturbed lagoons. 相似文献
120.
It has been recently shown numerically that sex enables selection for alleles that perform well across different genetic contexts, i.e., selection for mixability. Here we capture this result analytically in a simple case. This serves a dual purpose. First, it provides a clear distinction between fitness maximization and selection for mixability. Second, it points out a limitation of the traditional analytical approach as applied to mixability. 相似文献