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961.
Raúl Pérez-Ruiz Olga Hinze J?rg-M Neud?rfl Dirk Blunk Helmut G?rner Axel G Griesbeck 《Photochemical & photobiological sciences》2008,7(7):782-788
The solution photochemistry of the ortho allyloxy-substituted benzophenone has been investigated in detail. Product analysis revealed formation of a diastereomeric mixture of dihydrobenzofuran derivatives by cyclization via a short-lived intermediate 1,5-biradical and an unusual acetal by a pseudo-Paternò-Büchi rearrangement. The latter reaction pathway was supported by means of laser flash photolysis, where a long-lived intermediate with a maximum absorption band at 380 nm was observed. Besides, theoretical calculations (TD-DFT) of this UV-transient resulted in a band with maximum intensity at 390 nm showing a good correlation between experimental results and theoretical calculations. For comparison, the meta-substituent substrate was also investigated showing preferred triplet-triplet energy transfer. 相似文献
962.
Koczan D Drynda S Hecker M Drynda A Guthke R Kekow J Thiesen HJ 《Arthritis research & therapy》2008,10(3):R50
Introduction
About 30% of rheumatoid arthritis patients fail to respond adequately to TNFα-blocking therapy. There is a medical and socioeconomic need to identify molecular markers for an early prediction of responders and nonresponders. 相似文献963.
Marcus Jäger Frank Peter Tillmann Thomas S Thornhill Marcus Mahmoudi Dirk Blondin Rüdiger Gerd Hetzel Christoph Zilkens Rüdiger Krauspe 《Arthritis research & therapy》2008,10(5):1-14
Introduction
Bone marrow oedema (BME) and avascular osteonecrosis (AVN) are disorders of unclear origin. Although there are numerous operative and non-operative treatments for AVN, pain management in patients with AVN remains challenging. Prostaglandins play an important role in inflammatory responses and cell differentiation. It is thought that prostaglandin I2 ([PGI2] or synonoma prostacyclin) and its analogues promote bone regeneration on a cellular or systemic level. The purpose of this study was to assess the curative and symptomatic efficacy of the prostacyclin analogue iloprost in BME and AVN patients.Method
We are reporting on 50 patients (117 bones) affected by BME/AVN who were treated with iloprost. Pain levels before, during and 3 and 6 months after iloprost application were evaluated by a visual analogue scale (VAS). The short form(SF)-36 health survey served to judge general health status before and after treatment. Harris Hip Score (HHS) and Knee Society Score (KSS) were performed as functional scores and MRI and X-rays before and 3 and 6 months after iloprost application served as objective parameters for morphological changes of the affected bones.Results
We found a significant improvement in pain, functional and radiological outcome in BME and early AVN stages after iloprost application, whereas patients with advanced AVN stages did not benefit from iloprost infusions. Mean pain level decreased from 5.26 (day 0) to 1.63 (6 months) and both HHS and KSS increased during follow-up. Moreover, the SF-36 increased from 353.2 (day 0) to 560.5 points (6 months). We found a significant decrease in BME on MRI scans after iloprost application.Conclusions
In addition to other drugs, iloprost may be an alternative substance which should be considered in the treatment of BME/AVN-associated pain. 相似文献964.
Keap1/Nrf2 signaling defends organisms against the detrimental effects of oxidative stress and has been suggested to abate its consequences, including aging-associated diseases like neurodegeneration, chronic inflammation, and cancer. Nrf2 is a prominent target for drug discovery, and Nrf2-activating agents are in clinical trials for cancer chemoprevention. However, aberrant activation of Nrf2 by keap1 somatic mutations may contribute to carcinogenesis and promote resistance to chemotherapy. To evaluate potential functions of Keap1 and Nrf2 for organismal homeostasis, we characterized the pathway in Drosophila. We demonstrate that Keap1/Nrf2 signaling in the fruit fly is activated by oxidants, induces antioxidant and detoxification responses, and confers increased tolerance to oxidative stress. Importantly, keap1 loss-of-function mutations extend the lifespan of Drosophila males, supporting a role for Nrf2 signaling in the regulation of longevity. Interestingly, cancer chemopreventive drugs potently stimulate Drosophila Nrf2 activity, suggesting the fruit fly as an experimental system to identify and characterize such agents. 相似文献
965.
Libnow S Methling K Hein M Michalik D Harms M Wende K Flemming A Köckerling M Reinke H Bednarski PJ Lalk M Langer P 《Bioorganic & medicinal chemistry》2008,16(10):5570-5583
The first indirubin-N'-glycosides were prepared based on reactions of isatin-N'-glycosides with indoxyls. The products show a significant anti-proliferative activity against various human cancer cell lines. Good results were observed for an indirubin-N'-mannoside which was shown to have medium to high anti-proliferative activity against all investigated cell lines. The highest activities and selectivities against the MCF-7 breast cancer cell line were observed for indirubin-N'-rhamnosides. 相似文献
966.
Haemers T Wiesner J Giessmann D Verbrugghen T Hillaert U Ortmann R Jomaa H Link A Schlitzer M Van Calenbergh S 《Bioorganic & medicinal chemistry》2008,16(6):3361-3371
To expand the structure-activity relationships of fosmidomycin and FR900098, two potent antimalarials interfering with the MEP-pathway, we decided to replace a methylene group in beta-position of the phosphonate moiety of these leads by an oxygen atom. beta-oxa-FR900098 (11) proved equally active as the parent compound. When applied to 4-[hydroxyl(methyl)amino]-4-oxobutyl phosphonic acid, featuring a hydroxamate instead of the retrohydroxamate moiety, a beta-oxa modification yielded a derivative (13) with superior activity against the Plasmodium falciparum 3D7 strain than fosmidomycin, while a gamma-oxa modification resulted in less active derivatives. A bis(pivaloyloxymethyl)ester of phosphonate 13 proved twice as active in inhibiting cultured parasites as a similar prodrug of FR900098. 相似文献
967.
Rewinkel J Enthoven M Golstein I van der Rijst M Scholten A van Tilborg M de Weys D Wisse J Hamersma H 《Bioorganic & medicinal chemistry》2008,16(6):2753-2763
Recently, a new class (often referred to as SPRMs: selective progesterone receptor modulators) of progesterone receptor ligands with mixed agonist/antagonist properties has been described. Such compounds are envisaged, for example, as treatment for endometriosis, uterine fibroids, and leiomyomas. Existing SPRMs include Asoprisnil 1 and Uliprisnil acetate 2. In our hands, however, these compounds proved to have a predominantly or exclusively antagonistic in vitro profile, which may make this type of compound less attractive, for example, as contraceptives. We therefore aimed at a class of mixed-profile compounds that would show a more evenly balanced agonist/antagonist profile. A novel class of 11beta-[4-(heteroaryl)phenyl]-substituted pregnanes was identified that displayed the desired balance. Contrary to known SPRMs, this novel class of MPP (mixed-profile progestagen) was found to have a truly mixed activity, including a sizeable agonist component. 相似文献
968.
We studied the short-term impact of sediment load on the photosynthetic performance of Saccharina latissima sporophytes exposed to ultraviolet radiation (UVR). The algae were collected from different sediment-influenced environments
in Svalbard in August 2007. Initial optimum quantum yield (F
v/F
m) of sediment-covered sporophytes was significantly higher compared to sediment-free sporophytes. Experimental sediment coating
on blade discs had a photoprotective function by screening out 92% of the weighted UV-B (UVery) treatment. No UVR-induced photoinhibition was observed in sediment-coated blade discs while sediment removal caused a reduction
in F
v/F
m not only after 12-h UVR exposure but also after 6-h recovery in low white light compared to the initial value. Thus, sediment
coating has a short-term functional significance in mitigating the negative effect of UVR on photosynthesis of an important
kelp species and set a baseline for further studies.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
969.
970.
The PRA1 gene family in Arabidopsis 总被引:1,自引:0,他引:1
Alvim Kamei CL Boruc J Vandepoele K Van den Daele H Maes S Russinova E Inzé D De Veylder L 《Plant physiology》2008,147(4):1735-1749
Prenylated Rab acceptor 1 (PRA1) domain proteins are small transmembrane proteins that regulate vesicle trafficking as receptors of Rab GTPases and the vacuolar soluble N-ethylmaleimide-sensitive factor attachment receptor protein VAMP2. However, little is known about PRA1 family members in plants. Sequence analysis revealed that higher plants, compared with animals and primitive plants, possess an expanded family of PRA1 domain-containing proteins. The Arabidopsis (Arabidopsis thaliana) PRA1 (AtPRA1) proteins were found to homodimerize and heterodimerize in a manner corresponding to their phylogenetic distribution. Different AtPRA1 family members displayed distinct expression patterns, with a preference for vascular cells and expanding or developing tissues. AtPRA1 genes were significantly coexpressed with Rab GTPases and genes encoding vesicle transport proteins, suggesting an involvement in the vesicle trafficking process similar to that of their animal counterparts. Correspondingly, AtPRA1 proteins were localized in the endoplasmic reticulum, Golgi apparatus, and endosomes/prevacuolar compartments, hinting at a function in both secretory and endocytic intracellular trafficking pathways. Taken together, our data reveal a high functional diversity of AtPRA1 proteins, probably dealing with the various demands of the complex trafficking system. 相似文献