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941.
García-Mayoral MF Hollingworth D Masino L Díaz-Moreno I Kelly G Gherzi R Chou CF Chen CY Ramos A 《Structure (London, England : 1993)》2007,15(4):485-498
The AU-rich element (ARE) RNA-binding protein KSRP (K-homology splicing regulator protein) contains four KH domains and promotes the degradation of specific mRNAs that encode proteins with functions in cellular proliferation and inflammatory response. The fourth KH domain (KH4) is essential for mRNA recognition and decay but requires the third KH domain (KH3) for its function. We show that KH3 and KH4 behave as independent binding modules and can interact with different regions of the AU-rich RNA targets of KSRP. This provides KSRP with the structural flexibility needed to recognize a set of different targets in the context of their 3'UTR structural settings. Surprisingly, we find that KH4 binds to its target AREs with lower affinity than KH3 and that KSRP's mRNA binding, and mRNA degradation activities are closely associated with a conserved structural element of KH4. 相似文献
942.
943.
Regulation of the CAMP gene by 1,25(OH)2D3 in various tissues 总被引:1,自引:0,他引:1
Adrian F. Gombart James OKelly Tsuyako Saito H. Phillip Koeffler 《The Journal of steroid biochemistry and molecular biology》2007,103(3-5):552
The induction of antimicrobial peptides such as the human cathelicidin, CAMP/hCAP18, by 1,25(OH)2D3 provides a very exciting therapeutic approach in boosting immunity against infectious diseases. To explore the range of cell types and expand the number of cell models for studying the regulation of CAMP gene expression by 1,25(OH)2D3, we treated cell lines from various tissue types and determined CAMP gene expression. Also, we tested additional compounds together with 1,25(OH)2D3 to look for possible cooperative activation of the gene. We identified 1,25(OH)2D3-mediated induction of the CAMP gene in B-cell lymphomas, prostate and endometrial cancer lines and found cooperative activation with the histone deacetylase inhibitor sodium butyrate. The data suggest that regulation of CAMP by 1,25(OH)2D3 is potentially important in a wide range of tissues. 相似文献
944.
Geisler J Haynes B Ekse D Dowsett M Lønning PE 《The Journal of steroid biochemistry and molecular biology》2007,104(1-2):27-34
The adipocytokine leptin has recently been shown to enhance the expression of aromatase via promoter II and I.3 using an AP-1 motif. Thus, we evaluated the correlation between plasma leptin concentrations and total body aromatization (TBA) as well as plasma levels of estrone (E(1)), estradiol (E(2)) and estrone sulfate (E(1)S) in postmenopausal breast cancer patients. Twenty-two postmenopausal women with metastatic breast cancer, participating in tracer studies for the measurement of total body aromatization (TBA) in vivo, were available. In addition, blood samples for plasma estrogens and leptin measurements were available from another 22 breast cancer patients and 114 healthy postmenopausal women participating in the mammography-screening program. Values for TBA varied from 1.46 to 4.72% while plasma leptin levels ranged from 1.83 to 95.51 ng/ml in the same group of patients. All plasma estrogen levels were in the normal range expected for postmenopausal women. We found a significant correlation between pretreatment leptin levels and TBA (r(s) 0.452, P=0.01). In contrast, basal levels of TBA did not correlate to body mass index (BMI) in the same group of patients. Plasma leptin levels correlated to plasma levels of estradiol (r(s) 0.659, P=0.007), and estrone sulfate (r(s) 0.562, P=0.01) in the group of breast cancer patients (n=44) as well as in the group of healthy postmenopausal women (estradiol, r(s) 0.363, P< or =0.001, estrone sulfate r(s) 0.353, P< or =0.001). In conclusion, we found plasma leptin levels to correlate to TBA in breast cancer patients and to plasma levels of estradiol and estrone sulfate in breast cancer patients as well as in healthy postmenopausal females. These findings suggest that leptin may influence on aromatase activity in vivo, providing a possible link between body weight and plasma estrogen levels as well as breast cancer risk. 相似文献
945.
Musonda CC Little S Yardley V Chibale K 《Bioorganic & medicinal chemistry letters》2007,17(17):4733-4736
The synthesis and antimalarial activity of a novel series of first generation 4-aminoquinoline-containing 2,4,5-trisubstituted aminoxazoles against two strains of the Plasmodium falciparum parasite in vitro is described. A number of compounds significantly more potent than the standard drug chloroquine were identified. 相似文献
946.
Biot C Pradines B Sergeant MH Gut J Rosenthal PJ Chibale K 《Bioorganic & medicinal chemistry letters》2007,17(23):6434-6438
The design, synthesis, and antimalarial activity of chimeras of thiosemicarbazones (TSC) and ferroquine (FQ) is reported. Key structural elements derived from FQ were coupled to fragments capable of coordinating metal ions. Biological evaluation was conducted against four strains of the malaria parasite Plasmodium falciparum and against the parasitic cysteine protease falcipain-2. To establish the role of the ferrocenyl moiety in the antiplasmodial activity of this series, purely organic parent compounds were also synthesized and tested. The presence of the aminoquinoline structure, allowing transport of the compounds to the food vacuole of the parasite, seems to be the major contributor to antimalarial activity. 相似文献
947.
Lafontaine JA Day RF Dibrino J Hadcock JR Hargrove DM Linhares M Martin KA Maurer TS Nardone NA Tess DA Dasilva-Jardine P 《Bioorganic & medicinal chemistry letters》2007,17(18):5245-5250
A novel series of heterocycle-based analogs were prepared and evaluated for their in vitro and in vivo biological activity as human beta(3)-adrenergic receptor (AR) agonists. Several analogs demonstrated potent agonist activity at the beta(3)-AR, functional selectivity against beta(1)- and beta(2)-ARs, and favorable pharmacokinetic profiles in vivo. Compound 17 increased oxygen consumption in rats, a measure of energy expenditure, with an ED(20%) of 2mg/kg. 相似文献
948.
Glaros AG Kim-Weroha N Lausten L Franklin KL 《Applied psychophysiology and biofeedback》2007,32(3-4):149-154
This study tested the hypothesis that a habit reversal program emphasizing awareness and reduction of masticatory muscle activity
would significantly reduce pain in patients diagnosed with chronic temporomandibular disorder (TMD) and would be a competitive
alternative to a behaviorally-modified dental intervention. Eight individuals diagnosed with TMD were randomly assigned to
a splint therapy or habit reversal group. Patients in the splint group received an interocclusal appliance (splint) fabricated
from acrylic and were instructed to wear the splint day and night up to a maximum of 20 h per day. Patients in the habit reversal
group were given a pager and instructed to check tooth position and masticatory muscle tension when paged. Paging occurred
approximately once every 2 h during the day, but not at night. Both groups were instructed to avoid tooth contact and relax
the masticatory muscles during the 4 weeks of active treatment. Outcome data were collected at 1 month and 1 year post-treatment
intervals. Pain decreased significantly for both groups and did not differ between groups. Habit reversal may be as effective
as a behaviorally-modified splint therapy for TMD-related pain. 相似文献
949.
R-type pyocin is a bacteriophage tail-shaped bacteriocin produced by Pseudomonas aeruginosa, but its physiological roles are relatively unknown. Here we describe a role of R-type pyocin in the competitive growth advantages between P. aeruginosa strains. Partial purification and gene disruption revealed that the major killing activity from the culture supernatant of PA14 is attributed to R-type pyocin, neither F-type nor S-type pyocins. These findings may provide insight into the forces governing P. aeruginosa population dynamics to promote and maintain its biodiversity. 相似文献
950.
Model-based, three-dimensional (3D) image reconstruction procedures require a starting model to initiate data analysis. We have designed an ab initio method, which we call the random model (RM) method, that automatically generates models to initiate structural analysis of icosahedral viruses imaged by cryo-electron microscopy. The robustness of the RM procedure was demonstrated on experimental sets of images for five representative viruses. The RM method also provides a straightforward way to generate unbiased starting models to derive independent 3D reconstructions and obtain a more reliable assessment of resolution. The fundamental scheme embodied in the RM method should be relatively easy to integrate into other icosahedral software packages. 相似文献