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931.
Andrechek ER Mori S Rempel RE Chang JT Nevins JR 《Development (Cambridge, England)》2008,135(14):2403-2413
Previous work has detailed the histological and biochemical changes associated with mammary development and remodeling. We have now made use of gene expression profiling, and in particular of the previously described signatures of cell signaling pathway activation, to explore the events associated with mammary gland development. We find that there is elevated E2F-specific pathway activity prior to lactation and relatively low levels of other important signaling pathways, such as RAS, MYC and SRC. Upon lactation and continuing into the involution phase, these patterns reverse with a dramatic increase in RAS, SRC and MYC pathway activity and a decline in E2F activity. At the end of involution, these patterns return to that of the adult non-lactating mammary gland. The importance of the changes in E2F pathway activity, particularly during the proliferative phase of mammary development, was confirmed through the analysis of mice deficient for various E2F proteins. Taken together, these results reveal a complex pattern of pathway activity in relation to the various phases of mammary gland development. 相似文献
932.
933.
Elman NM Ben-Yoav H Sternheim M Rosen R Krylov S Shacham-Diamand Y 《Biosensors & bioelectronics》2008,23(11):1631-1636
A lab-on-chip consisting of a unique integration of whole-cell sensors, a MOEMS (Micro-Opto-Electro-Mechanical-System) modulator, and solid-state photo-detectors was implemented for the first time. Whole-cell sensors were genetically engineered to express a bioluminescent reporter (lux) as a function of the lac promoter. The MOEMS modulator was designed to overcome the inherent low frequency noise of solid-state photo-detectors by means of a previously reported modulation technique, named IHOS (Integrated Heterodyne Optical System). The bio-reporter signals were modulated prior to photo-detection, increasing the SNR of solid-state photo-detectors at least by three orders of magnitude. Experiments were performed using isopropyl-beta-d-thiogalactopyranoside (IPTG) as a preliminary step towards testing environmental toxicity. The inducer was used to trigger the expression response of the whole-cell sensors testing the sensitivity of the lab-on-chip. Low intensity bio-reporter optical signals were measured after the whole-cell sensors were exposed to IPTG concentrations of 0.1, 0.05, and 0.02 mM. The experimental results reveal the potential of this technology for future implementation as an inexpensive massive method for rapid environmental toxicity detection. 相似文献
934.
935.
Ruth H. Leeney Rachel Amies Annette C. Broderick Matthew J. Witt Jan Loveridge Joana Doyle Brendan J. Godley 《Biodiversity and Conservation》2008,17(10):2323-2338
Marine vertebrate strandings data can provide insights into the long-term dynamics of cetacean populations, and the threats
they face. We investigate whether the spatio-temporal patterns of cetacean strandings around Cornwall, SW Britain, have changed
in the past century. Analysis of strandings from 1911 to 2006 (n = 2,257) show that, since the mid-1970s, the relative frequency of strandings of common dolphins (Delphinus delphis), harbour porpoises (Phocoena phocoena) and pilot whales (Globicephala melas) has increased significantly. Seasonal peaks in strandings frequencies are apparent, between December and March for harbour
porpoises and common dolphins, and between November and January for pilot whales. There were significant positive trends in
the number of common dolphin and harbour porpoise strandings, as a proportion of total strandings, over time. Strandings of
common dolphins, porpoises and all other species occur more frequently on the south coast of Cornwall. A total of 415 cetaceans
were subject to full veterinary necropsy to determine cause of death, between 1990 and 2006, and 253 (61%) of these individuals
were determined to have died due to bycatch in fishing gear. Analyses of industrialised fishing pressure in UK waters show
the seas around Cornwall to be one of the most heavily fished areas of the UK. We suggest a number of factors that could be
responsible for the recent increases in cetacean strandings in southwest UK waters in recent years, including survey effort,
as well as abundance and range shifts that are potentially linked with climate change. Although detectable levels of bycatch
rate have not increased over time, fisheries interactions are in significant part responsible for mortality patterns and are
worthy of more detailed investigation.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
936.
Davidovich-Rikanati R Lewinsohn E Bar E Iijima Y Pichersky E Sitrit Y 《The Plant journal : for cell and molecular biology》2008,56(2):228-238
alpha-Zingiberene synthase (ZIS), a sesquiterpene synthase gene that was isolated from lemon basil (Ocimum basilicum L.), encodes an enzyme that catalyzes the formation of alpha-zingiberene, and other sesquiterpenes, from farnesyl diphosphate. Transgenic tomato fruits overexpressing ZIS under the control of the fruit ripening-specific tomato polygalacturonase promoter (PG) accumulated high levels of alpha-zingiberene (224-1000 ng g(-1) fresh weight) and other sesquiterpenes, such as alpha-bergamotene, 7-epi-sesquithujene, beta-bisabolene and beta-curcumene, whereas no sesquiterpenes were detected in non-transformed control fruits. The ZIS-transgenic fruits also produced monoterpenes, such as alpha-thujene, alpha-pinene, beta-phellandrene and gamma-terpinene (1-22 ng g(-1) fresh weight), which were either not detected or were found only in minute concentrations in control fruits. Recombinant ZIS overexpressed in Escherichia coli catalyzed the formation of these monoterpenes from geranyl diphosphate. As the ZIS protein apparently lacks a transit peptide, and is localized in the cytosol, the production of monoterpenes in the transgenic tomatoes suggests that a pool of geranyl diphosphate is available in the cytosol. The phenotype of the ZIS-transgenic tomatoes was the same as that for wild-type tomatoes, with regard to plant vigor and shape, but transgenic plants exhibited a small decrease in lycopene content. This study thus showed that the synthesis of both mono- and sesquiterpenes can be enhanced by the ectopic expression of a single transgene in tomato fruit, and it further demonstrated the interconnection between the pools of terpenoid precursors in the plastids and the cytosol. 相似文献
937.
Clarke B Demont E Dingwall C Dunsdon R Faller A Hawkins J Hussain I MacPherson D Maile G Matico R Milner P Mosley J Naylor A O'Brien A Redshaw S Riddell D Rowland P Soleil V Smith KJ Stanway S Stemp G Sweitzer S Theobald P Vesey D Walter DS Ward J Wayne G 《Bioorganic & medicinal chemistry letters》2008,18(3):1017-1021
This paper describes the discovery of non-peptidic, potent, and selective hydroxy ethylamine (HEA) inhibitors of BACE-1 by replacement of the prime side of a lead di-amide 2. Inhibitors with nanosmolar potency and high selectivity were identified. Depending on the nature of the P(1)(') and P(2)(') substituents, two different binding modes were observed in X-ray co-crystal structures. 相似文献
938.
Rachel Weitzdoerfer Harald Hoeger Efrem Engidawork Mario Engelmann Nicolas Singewald Gert Lubec Barbara Lubec 《Nitric oxide》2004,10(3):130-140
Nitric oxide (NO) plays a role in a series of neurobiological functions, underlying behavior and memory. The functional role of nNOS derived NO in cognitive functions, however, is elusive. We decided to study cognitive functions in the Morris water maze (MWM) and the multiple T-maze (MTM) in 3-month-old male nNOS-knock-out mice (nNOS KO). To study the influence of neurology and behavior, we performed tests in an observational battery, the rota-rod, the elevated plus maze (EPM), the open field (OF), and a social interaction test. In the memory and relearning task of the MWM, most nNOS KO failed whereas performing better in the MTM. nNOS KO displayed significantly increased frequency of grooming, center crossings, and entries into the center in the OF. The observational battery revealed significantly increased scores for touch-escape reaction, body position, locomotion, and pelvic- and tail-elevation together with reduced vocalization. In the EPM, the time spent in the closed arm and the grooming frequency were significantly increased whereas urination was absent. We conclude that nNOS KO show impaired spatial performance in the MWM and herewith confirm the role of nNOS in cognitive functions such as processing, maintenance, and recall of memory. It must be taken into account that the major behavioral findings of increased grooming and anxiety-related behaviors may have led to impaired function in the MWM. The fact that nNOS KO performed well in the MTM, reflecting a low stress situation points to the interpretation that nNOS inhibition affects cognitive functions under stressful conditions (MWM) only. 相似文献
939.
Ian R. Henderson Fernando Navarro-Garcia Micka?l Desvaux Rachel C. Fernandez Dlawer Ala'Aldeen 《Microbiology and molecular biology reviews》2004,68(4):692-744
Gram-negative bacteria possess an outer membrane layer which constrains uptake and secretion of solutes and polypeptides. To overcome this barrier, bacteria have developed several systems for protein secretion. The type V secretion pathway encompasses the autotransporter proteins, the two-partner secretion system, and the recently described type Vc or AT-2 family of proteins. Since its discovery in the late 1980s, this family of secreted proteins has expanded continuously, due largely to the advent of the genomic age, to become the largest group of secreted proteins in gram-negative bacteria. Several of these proteins play essential roles in the pathogenesis of bacterial infections and have been characterized in detail, demonstrating a diverse array of function including the ability to condense host cell actin and to modulate apoptosis. However, most of the autotransporter proteins remain to be characterized. In light of new discoveries and controversies in this research field, this review considers the autotransporter secretion process in the context of the more general field of bacterial protein translocation and exoprotein function. 相似文献
940.