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281.
Victoria?BrankinEmail author Marcus?RP?Mitchell Bob?Webb Morag?G?Hunter 《Reproductive biology and endocrinology : RB&E》2003,1(1):55
Oocyte control of granulosa and theca cell function may be mediated by several growth factors via a local feedback loop(s)
between these cell types. This study examined both the role of oocyte-secreted factors on granulosa and thecal cells, cultured
independently and in co-culture, and the effect of stem cell factor (SCF); a granulosa cell derived peptide that appears to
have multiple roles in follicle development. Granulosa and theca cells were isolated from 2–6 mm healthy follicles of mature
porcine ovaries and cultured under serum-free conditions, supplemented with: 100 ng/ml LR3 IGF-1, 10 ng/ml insulin, 100 ng/ml
testosterone, 0–10 ng/ml SCF, 1 ng/ml FSH (granulosa), 0.01 ng/ml LH (theca) or 1 ng/ml FSH and 0.01 ng/ml LH (co-culture)
and with/without oocyte conditioned medium (OCM) or 5 oocytes. Cells were cultured in 96 well plates for 144 h, after which
viable cell numbers were determined. Medium was replaced every 48 h and spent medium analysed for steroids. 相似文献
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The Ku heterodimer performs separable activities at double-strand breaks and chromosome termini
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The Ku heterodimer functions at two kinds of DNA ends: telomeres and double-strand breaks. The role that Ku plays at these two classes of termini must be distinct, because Ku is required for accurate and efficient joining of double-strand breaks while similar DNA repair events are normally prohibited at chromosome ends. Toward defining these functional differences, we have identified eight mutations in the large subunit of the Saccharomyces cerevisiae Ku heterodimer (YKU80) which retain the ability to repair double-strand breaks but are severely impaired for chromosome end protection. Detailed characterization of these mutations, referred to as yku80(tel) alleles, has revealed that Ku performs functionally distinct activities at subtelomeric chromatin versus the end of the chromosome, and these activities are separable from Ku's role in telomere length regulation. While at the chromosome terminus, we propose that Ku participates in two different activities: it facilitates telomerase-mediated G-strand synthesis, thereby contributing to telomere length regulation, and it separately protects against resection of the C-strand, thereby contributing to protection of chromosome termini. Furthermore, we propose that the Ku heterodimer performs discrete sets of functions at chromosome termini and at duplex subtelomeric chromatin, via separate interactions with these two locations. Based on homology modeling with the human Ku structure, five of the yku80(tel) alleles mutate residues that are conserved between the yeast and human Ku80 proteins, suggesting that these mutations probe activities that are shared between yeast and humans. 相似文献
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286.
Chai W Breitenbucher JG Kwok A Li X Wong V Carruthers NI Lovenberg TW Mazur C Wilson SJ Axe FU Jones TK 《Bioorganic & medicinal chemistry letters》2003,13(10):1767-1770
Continued exploration of the SAR around the lead imidazopyridine histamine H(3) antagonist 1 has led to the discovery of several related series of heterocyclic histamine H(3) antagonists. The synthesis and SAR of indolizine, indole and pyrazolopyridine based compounds are now described. 相似文献
287.
Sum FW Wong V Han S Largis E Mulvey R Tillett J 《Bioorganic & medicinal chemistry letters》2003,13(13):2191-2194
Piperidine, pyrrolidine, and azetidine sulfonamides were examined as linkers in designing novel human beta(3) adrenergic receptor (beta(3)-AR) agonists. The azetidine derivative 37, and piperidine derivatives 7, 8, and 13 were found to be potent beta(3)-AR agonists and have good selectivity against beta(1)- and beta(2)-AR. 相似文献
288.
The respiratory chain enzymes of microaerophilic bacteria should play a major role in their adaptation to growth at low oxygen tensions. The genes encoding the putative NADH:quinone reductases (NDH-1), the ubiquinol:cytochrome c oxidoreductases (bc1 complex) and the terminal oxidases of the microaerophiles Campylobacter jejuni and Helicobacter pylori were analysed to identify structural elements that may be required for their unique energy metabolism. The gene clusters encoding NDH-1 in both C. jejuni and H. pylori lacked nuoE and nuoF, and in their place were genes encoding two unknown proteins. The NuoG subunit in these microaerophilic bacteria appeared to have an additional Fe-S cluster that is not present in NDH-1 from other organisms; but C. jejuni and H. pylori differed from each other in a cysteine-rich segment in this subunit, which is present in some but not all NDH-1. Both organisms lacked genes orthologous to those encoding NDH-2. The subunits of the bc1 complex of both bacteria were similar, and the Rieske Fe-S and cytochrome b subunits had significant similarity to those of Paracoccus denitrificans and Rhodobacter capsulatus, well-studied bacterial bc1 complexes. The composition of the terminal oxidases of C. jejuni and H. pylori was different; both bacteria had cytochrome cbb3 oxidases, but C. jejuni also contained a bd-type quinol oxidase. The primary structures of the major subunits of the cbb3-type (terminal) oxidase of C. jejuni and H. pylori indicated that they form a separate group within the cbb3 protein family. The implications of the results for the function of the enzymes and their adaptation to microaerophilic growth are discussed. 相似文献
289.
Induction of antitumor immunity by indomethacin 总被引:4,自引:0,他引:4
Morecki S Yacovlev E Gelfand Y Trembovler V Shohami E Slavin S 《Cancer immunology, immunotherapy : CII》2000,48(11):613-620
Irradiated tumor cells given, together with indomethacin, to syngeneic mice induced an antitumor response and conferred protection
against a challenge of a lethal dose of murine mammary (4T1) and lung (3LL) carcinoma cells. Continuous administration of
indomethacin was crucial throughout the entire period of immunization and challenge, as no protection was achieved when the
drug was given during only one of these procedures. Antitumor immunity was long-lasting and, when tested in the 4T1 model,
48% of mice were resistant to a second challenge of lethal tumor cells. Tumor-free immune mice that were given indomethacin
for more than 300 days remained healthy with normal white blood cell counts and normal spleen size. Cells isolated from immune
mice were able to kill tumor cells in culture after in vitro activation by interleukin-2, in a manner similar to cells from
naive normal control mice. In addition, the mitogenic response of their T cells was as high as that of the control naive mice.
While indomethacin was able to induce antitumor immunity to 4T1 and 3LL murine carcinoma cells, both of which contain a high
concentration of endogenic prostaglandin E2 (PGE2), no such immunity was achieved to murine tumor cells with a low concentration of endogenic PGE2. These results suggest
a correlation between PGE2 concentration and the ability of indomethacin to induce antitumor immunity. We therefore suggest
that an immunotherapy protocol with long-term dispensation of a tolerable dose of an immunomodulator, given together with
irradiated autologous tumor cells, may stimulate antitumor responses to tumors containing high concentrations of endogenic
PGE2.
Received: 12 August 1999 / Accepted: 21 September 1999 相似文献
290.