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61.
《Bioorganic & medicinal chemistry》2014,22(15):3913-3921
A series of furazan and furoxan sulfonamides were prepared and studied for their ability to inhibit human carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I, hCA II, hCA IX, and hCA XII. The simple methyl substituted products 3–5 were potent inhibitors. Differing structural modifications of these leads had differing effects on potency and selectivity. In particular, products in which the sulfonamide group is separated from the hetero ring by a phenylene bridge retained high potency only on the hCA XII isoform. The sulfonamides 3–5 exerted intraocular pressure (IOP) lowering effects in vivo in hypertensive rabbits more efficiently than dorzolamide. Some other products (39–42), although less effective in vitro hCA II/XII inhibitors, also effectively lowered IOP in two different animal models of glaucoma. 相似文献
62.
63.
《Molecular & cellular proteomics : MCP》2023,22(1):100480
Alternative ORFs (AltORFs) are unannotated sequences in genome that encode novel peptides or proteins named alternative proteins (AltProts). Although ribosome profiling and bioinformatics predict a large number of AltProts, mass spectrometry as the only direct way of identification is hampered by the short lengths and relative low abundance of AltProts. There is an urgent need for improvement of mass spectrometry methodologies for AltProt identification. Here, we report an approach based on size-exclusion chromatography for simultaneous enrichment and fractionation of AltProts from complex proteome. This method greatly simplifies the variance of AltProts discovery by enriching small proteins smaller than 40 kDa. In a systematic comparison between 10 methods, the approach we reported enabled the discovery of more AltProts with overall higher intensities, with less cost of time and effort compared to other workflows. We applied this approach to identify 89 novel AltProts from mouse liver, 39 of which were differentially expressed between embryonic and adult mice. During embryonic development, the upregulated AltProts were mainly involved in biological pathways on RNA splicing and processing, whereas the AltProts involved in metabolisms were more active in adult livers. Our study not only provides an effective approach for identifying AltProts but also novel AltProts that are potentially important in developmental biology. 相似文献
64.
65.
Native chemical ligation has enabled the chemical synthesis of proteins for a wide variety of applications (e.g., mirror-image proteins). However, inefficiencies of this chemoselective ligation in the context of large or otherwise challenging protein targets can limit the practical scope of chemical protein synthesis. In this review, we focus on recent developments aimed at enhancing and expanding native chemical ligation for challenging protein syntheses. Chemical auxiliaries, use of selenium chemistry, and templating all enable ligations at otherwise suboptimal junctions. The continuing development of these tools is making the chemical synthesis of large proteins increasingly accessible. 相似文献
66.
The effect of different carbon and nitrogen sources on the production of toxin by Clostridium argentinense was examined. The toxin production by C. argentinense in coculture with Pseudomonas mendocina increased in all the cases in relation to that produced by monocultures independent of the nature of the source. Using dextrin as carbon source C. argentinense produced the highest levels of toxin both in monocultures (300 LD50/mL) and in cocultures with P. mendocina (5000 LD50/mL). Experiments run in a microfermenter showed that the slow growth of cocultures associated with the assimilation of dextrin and the pH and Eh profiles favoured the production of toxin. Of the nitrogen sources assayed, corn steep liquor sustained the highest levels of toxin in both monocultures and cocultures with 3 and 2.8 fold increases with respect to that obtained using proteose peptone. The toxin production by C. argentinense cultures and C. argentinense–P. mendocina cocultures was highly dependent on the nature of the carbon and nitrogen sources used in the culture media. Growth of C. argentinense on substrates slowly assimilated stimulated the production of toxin. 相似文献
67.
Understanding the mechanisms of resilience of coral reefs to anthropogenic stressors is a critical step toward mitigating their current global decline. Coral–bacteria associations are fundamental to reef health and disease, but direct observations of these interactions remain largely unexplored. Here, we use novel technology, high-speed laser scanning confocal microscopy on live coral (Pocillopora damicornis), to test the hypothesis that corals exert control over the abundance of their associated bacterial communities by releasing (‘shedding'') bacteria from their surface, and that this mechanism can counteract bacterial growth stimulated by organic inputs. We also test the hypothesis that the coral pathogen Vibrio coralliilyticus can evade such a defense mechanism. This first report of direct observation with high-speed confocal microscopy of living coral and its associated bacterial community revealed a layer (3.3–146.8 μm thick) on the coral surface where bacteria were concentrated. The results of two independent experiments showed that the bacterial abundance in this layer was not sensitive to enrichment (5 mg l−1 peptone), and that coral fragments exposed to enrichment released significantly more bacteria from their surfaces than control corals (P<0.01; 35.9±1.4 × 105 cells cm−2 coral versus 1.3±0.5 × 105 cells cm−2 coral). Our results provide direct support to the hypothesis that shedding bacteria may be an important mechanism by which coral-associated bacterial abundances are regulated under organic matter stress. Additionally, the novel ability to watch this ecological behavior in real-time at the microscale opens an unexplored avenue for mechanistic studies of coral–microbe interactions. 相似文献
68.
69.
Fire can cause severe nitrogen (N) losses from grassland, chaparral, and temperate and boreal forest ecosystems. Paradoxically,
soil ammonium levels are markedly increased by fire, resulting in high rates of primary production in re-establishing plant
communities. In a manipulative experiment, we examined the influence of wild-fire ash residues on soil, microbial and plant
N pools in a recently burned Californian bishop pine (Pinus muricata D. Don) forest. Ash stimulated post-fire primary production and ecosystem N retention through direct N inputs from ash to
soils, as well as indirect ash effects on soil N availability to plants. These results suggest that redistribution of surface
ash after fire by wind or water may cause substantial heterogeneity in soil N availability to plants, and could be an important
mechanism contributing to vegetation patchiness in fire-prone ecosystems. In addition, we investigated the impact of fire
on ecosystem N cycling by comparing 15N natural abundance values from recently burned and nearby unburned P. muricata forest communities. At the burned site, 15N natural abundance in recolonising species was similar to that in bulk soil organic matter. By contrast, there was a marked
15N depletion in the same species relative to the total soil N pool at the unburned site. These results suggest that plant uptake
of nitrate (which tends to be strongly depleted in 15N because of fractionation during nitrification) is low in recently burned forest communities but could be an important component
of eco- system N cycling in mature conifer stands.
Received: 29 June 1999 / Accepted: 24 October 1999 相似文献
70.
Floral organogenesis of Chloranthus sessilifolius K. F. Wu is described. The inflorescence primordium is dome-like in the beginning and then elongates, and bract primordia
initiate almost decussately. Each floral primordium, arising from the axil of a bract, soon becomes a scale-like structure,
with three primordia of androecial lobes originating from its abaxial part, and the gynoecial primordium in adaxial position.
As the androecial lobes become more distinct, four thecae are already in differentiation, and the gynoecial primordium appears
as a shallow disc. The androecial lobes do not extend their length until the thecae approach maturity and the stigma is differentiated.
The androecial lobes are united at all the stages of development, and the entire androecium falls off as a unit at the end
of anthesis. Based on these results, combined with published evidence from neobotany, palaeobotany and phylogenetic studies,
the morphological nature of the androecium of Chloranthus is further discussed. Our studies support the viewpoint that the androecial structure of Chloranthus may have arisen by splitting of a single stamen with 2 marginal thecae.
Received May 2, 2001 Accepted December 18, 2001 相似文献