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991.
Xu L Yang L Moitra PK Hashimoto K Rallabhandi P Kaul S Meroni G Jensen JP Weissman AM D'Arpa P 《Experimental cell research》2003,288(1):84-93
We previously identified BTBD1 and BTBD2 as novel topoisomerase I-interacting proteins that share 80% amino acid identity. Here we report the characterization of their subcellular localization. In a number of mouse and human cells, BTBD1 and BTBD2 (BTBD1/2) colocalized to punctate or elongated cytoplasmic bodies (< 5 microm long and several per cell) that were larger and more elongated in cancer cell lines than in fibroblasts and myoblasts. A search for potential colocalizing proteins identified TRIM family members that localize to morphologically similar cytoplasmic bodies, which were then tested for colocalization with BTBD1/2. TRIM5delta, expressed as a GFP fusion, colocalized with BTBD1/2 immunostaining and appeared to serve as a scaffold for the assembly of endogenous BTBD1/2 proteins. TRIM family members contain a RING domain, B-box(es), and coiled-coil regions, which have a characteristic order and spacing (RBCC domain). RING-dependent ubiquitin ligase activity and multimerization via the coiled-coil region may be defining properties of the RBCC/TRIM protein family. We found that TRIM5delta with a deleted coiled-coil region or a mutated RING domain failed to colocalize with BTBD1/2. Additionally, TRIM5delta ubiquitylated itself in a RING finger- and UbcH5B-dependent manner. BTBD1/2 each contain a PHR-similarity region, repeated twice on the putative ubiquitin ligases PAM, highwire and RPM-1, which also contain a RING and B-box. Thus, four protein modules found on each of these putative ubiquitin ligases, a RING, a B-box and two PHR repeats, are present on BTBD1/2 and TRIM5delta that are colocalized to cytoplasmic bodies. 相似文献
992.
Overexpressed mortalin (mot-2)/mthsp70/GRP75 and hTERT cooperate to extend the in vitro lifespan of human fibroblasts 总被引:8,自引:0,他引:8
The lifespan of human foreskin fibroblasts (HFF5), cultured under standard in vitro conditions (including ambient atmospheric oxygen tension), was extended slightly by expression of exogenous mortalin (mot-2)/mthsp70/Grp75, but not by the catalytic subunit of telomerase, hTERT. Together, mot-2 and hTERT permitted bypass of senescence, a substantial extension of lifespan, and possibly immortalization. This is the first demonstration that mot-2 and telomerase can cooperate in the immortalization process. 相似文献
993.
994.
Receptors for calcitonin gene-related peptide (CGRP), a neuropeptide known to be the most potent vasodilator, are abundantly expressed in cerebellum. A monoclonal antibody to cerebellar CGRP receptors specifically detects a 66 kDa protein from rat cerebellum and other rat and human tissues, but not from SK-N-MC cells which express calcitonin receptor-like receptor (CRLR), a recently described component of CGRP receptors. In contrast, mRNA expression for CRLR was abundant in SK-N-MC cells, but it was undetectable in rat cerebellum. Furthermore, the antibody could not detect any immunoreactive protein in HEK 293 cells transiently transfected with CRLR and receptor activity-modifying protein 1 (RAMP(1)) indicating the possible existence of another CGRP receptor, which does not involve CRLR. Due to the absence of biochemical or structural data on the existence of a CGRP(2) receptor and the new data provided in this paper, we suggest to identify the two CGRP receptors as CGRP-A and CGRP-B. 相似文献
995.
Choudhary S Cadier MA Shinn DL Shekhar K McDowall RA 《Plastic and reconstructive surgery》2003,111(2):576-82; discussion 583-5
There is a common concern that the Veau-Wardill-Kilner type of cleft palate repair causes extensive denudation of the palate, resulting in inhibition of maxillary growth. The evidence for this belief is equivocal in the literature. The authors present some long-term results of this technique from a pure sample of nonsyndromic complete unilateral cleft lip and palate patients operated on by a single intermediate-volume cleft surgeon over a period of 25 years. Twenty-five patients, all born between 1977 and 1989, met the above inclusion criteria. Their age at the time of collection of study models and cephalograms was 9 to 17 years (average, 12 years). Midfacial growth was studied using 12-year dental models and lateral cephalograms taken before definitive orthodontic treatment. These were evaluated using the GOSLON Yardstick and digital cephalometric analysis. The final GOSLON results show that 72 percent of the patients had a good or satisfactory outcome, with a GOSLON score of 1, 2, or 3, and only 28 percent ended with a poor score of 4 or 5. The poor sensitivity of cephalometrics in discerning statistically significant differences was highlighted by the huge overlaps observed in the 95 percent confidence interval graph of mean sella-nasion-subspinale angle (S-N-A) values when comparing the results of the Eurocleft centers with those of the authors' center. The results suggest that satisfactory long-term midfacial growth can be obtained with Veau-Wardill-Kilner cleft palate repair. 相似文献
996.
997.
998.
Targeted deletion reveals an essential function for the telomere length regulator Trf1 总被引:9,自引:0,他引:9 下载免费PDF全文
Karlseder J Kachatrian L Takai H Mercer K Hingorani S Jacks T de Lange T 《Molecular and cellular biology》2003,23(18):6533-6541
The human telomeric DNA binding factor TRF1 (hTRF1) and its interacting proteins TIN2, tankyrase 1 and 2, and PINX1 have been implicated in the regulation of telomerase-dependent telomere length maintenance. Here we show that targeted deletion of exon 1 of the mouse gene encoding Trf1 causes early (day 5 to 6 postcoitus) embryonic lethality. The absence of telomerase did not alter the Terf1(ex1Delta/ex1Delta) lethality, indicating that the phenotype was not due to inappropriate telomere elongation by telomerase. Terf1(ex1Delta/ex1Delta) blastocysts had a severe growth defect of the inner cell mass that was accompanied by apoptosis. However, no evidence was found for telomere uncapping causing this cell death; chromosome spreads of Terf1(ex1Delta/ex1Delta) blastocysts did not reveal chromosome end-to-end fusions, and p53 deficiency only briefly delayed Terf1(ex1Delta/ex1Delta) lethality. These data suggest that murine Trf1 has an essential function that is independent of telomere length regulation. 相似文献
999.
1000.
Ghosh J Basu A Pal S Chowdhuri S Bhattacharya A Pal D Chattoraj DK DasGupta C 《Molecular microbiology》2003,48(6):1679-1692
Bacterial ribosomes or their 50S subunit can refold many unfolded proteins. The folding activity resides in domain V of 23S RNA of the 50S subunit. Here we show that ribosomes can also refold a denatured chaperone, DnaK, in vitro, and the activity may apply in the folding of nascent DnaK polypeptides in vivo. The chaperone was unusual as the native protein associated with the 50S subunit stably with a 1:1 stoichiometry in vitro. The binding site of the native protein appears to be different from the domain V of 23S RNA, the region with which denatured proteins interact. The DnaK binding influenced the protein folding activity of domain V modestly. Conversely, denatured protein binding to domain V led to dissociation of the native chaperone from the 50S subunit. DnaK thus appears to depend on ribosomes for its own folding, and upon folding, can rebind to ribosome to modulate its general protein folding activity. 相似文献