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1.
The role of the epidermal growth factor-1 and hydrophobic stack domains of human factor IX in binding to endothelial cells. 总被引:6,自引:0,他引:6
W F Cheung D L Straight K J Smith S W Lin H R Roberts D W Stafford 《The Journal of biological chemistry》1991,266(14):8797-8800
To determine the function and specificity in factor IX of the first epidermal growth factor (EGF)-like domain and the eight-amino acid hydrophobic stack encoded by exon C (residues 39-46), these domains were replaced by the corresponding polypeptide regions of factor X and chimeric proteins were produced in human embryo kidney cells. Both chimeras were activated by factor XIa at a rate similar to plasma factor IX and exhibited calcium-dependent fluorescence quenching similar to plasma factor IX. Both chimeras competed equally for binding to the endothelial cell receptor. Our findings make it unlikely that the first EGF-like domain or the hydrophobic stack of factor IX are responsible for the specific binding of factor IX to its endothelial cell receptor. 相似文献
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Immortalization of hypothalamic GnRH neurons by genetically targeted tumorigenesis 总被引:47,自引:0,他引:47
By genetically targeting tumorigenesis to specific hypothalamic neurons in transgenic mice using the promoter region of the gonadotropin-releasing hormone (GnRH) gene to express the SV40 T-antigen oncogene, we have produced neuronal tumors and developed clonal, differentiated, neurosecretory cell lines. These cells extend neurites, express the endogenous mouse GnRH mRNA, release GnRH in response to depolarization, have regulatable fast Na+ channels found in neurons, and express neuronal, but not glial, cell markers. These immortalized cells will provide an invaluable model system for study of hypothalamic neurosecretory neurons that regulate reproduction. Significantly, their derivation demonstrates the feasibility of immortalizing differentiated neurons by targeting tumorigenesis in transgenic mice to specific neurons of the CNS. 相似文献
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M. N. Collinson Andrew M. Fisher Jean Walker Jane Currie Lisa Williams Paul Roberts 《Human genetics》1997,101(2):175-180
We present 33 families in which a pericentric inversion of chromosome 10 is segregating. In addition, we summarise the data
on 32 families in which an apparently identical inv(10) has been reported in the literature. Ascertainment was through prenatal
diagnosis or with a normal phenotype in 21/33 families. In the other 12 families, probands were ascertained through a wide
variety of referral reasons but in all but one case (a stillbirth), studies of the family showed that the reason for referral
was unrelated to the chromosome abnormality. There has been, to our knowledge, no recorded instance of a recombinant chromosome
10 arising from this inversion and no excess of infertility or spontaneous abortion among carriers of either sex. We propose
that inv(10)(p11.2q21.2) can be regarded as a variant analogous to the pericentric inversion of chromosome 2(p11q13). We conclude
that prenatal chromosome analysis is not justified for inv(10) carriers. In addition, family investigation of carrier status
is not warranted in view of the unnecessary concern this may cause parents and other family members.
Received: 7 July 1997 / Accepted: 4 August 1997 相似文献
6.
Santosh R. D'Mello Fabio Aglieco Melanie R. Roberts Kristin Borodezt John W. Haycock 《Journal of neurochemistry》1998,70(5):1809-1818
Abstract: Cultured cerebellar granule neurons undergo apoptosis when switched from a medium containing depolarizing levels of K+ (25 mM KCI) to medium containing lower levels of K+ (5 mM KCI). We used this paradigm to investigate the role of caspases in the death process. Two broad-spectrum caspase inhibitors, tert-butoxycarbonyl-Asp·(O-methyl)·fluoromethyl ketone and benzyloxycarbonyl-Val-Ala-Asp·fluoromethyl ketone, significantly reduced cell death (90 and 60%, respectively) at relatively low concentrations (10–25 µM), suggesting that caspase activation is involved in the apoptotic process. DNA fragmentation, a hallmark of apoptosis, was also reduced by these caspase inhibitors, suggesting that caspase activation occurred upstream of DNA cleavage in the sequence of events leading to cell death. As a step toward identifying the caspase(s) involved, the effects of N-acetyl Tyr-Val-Ala-Asp·chloromethyl ketone (YVAD·cmk), an interleukin-1β converting enzyme-preferring inhibitor, and N-acetyl Asp-Glu-Val-Asp·fluoromethyl ketone (DEVD·fmk), a CPP32-preferring inhibitor, were also evaluated. YVAD·cmk provided only modest (<20%) protection and only at the highest concentration (100 µM) tested, suggesting that interleukin-1β converting enzyme and/or closely related caspases were not involved. In comparison, DEVD·fmk inhibited cell death by up to 50%. Western blot analyses, however, failed to detect an increase in processing/activation of CPP32 or in the proteolysis of a CPP32 substrate, poly(ADP-ribose) polymerase, during the induction of apoptosis in granule neurons. Similarly, the levels of Nedd2, a caspase that is highly expressed in the brain and that is partially inhibited by DEVD·fmk, also remained unaffected in apoptotic neurons undergoing apoptosis. These results suggest that a DEVD-sensitive caspase other than CPP32 or Nedd2 mediates the induction of apoptosis in K+-deprived granule neurons. 相似文献
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D. F. Roberts 《International Journal of Anthropology》1996,11(2-4):185-191
As a conclusion, this paper reviews briefly the content of the volume. The wealth of demographic data has not been adequately
exploited in anthropology; this is why this publication is valuable in showing attempts to apply demographic data in a variety
of anthropological problems. This symposium has explored many interesting points which we recall here. Yet it has also opened
up a whole range of further questions on the material presented as well as in this broad field. Several directions of research
could be developed, for instance, testing among human populations, over long periods, the ecological thoughts of ecosystems
evolving as a cascade of instabilities, rather than a succession of equilibrium states. Let us also recall the pervasive nature
of demographic facts in topics such as the energy cycle or the genetic structure and evolution of human populations. 相似文献
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10.
We have earlier demonstrated that a mixed population of immunologically specific killer cells, including cytotoxic T lymphocytes, non-T (“B”) lymphocytes and monocytes, infiltrate “sponge matrix” allografts at the peak of rejection on Day 8 after transplantation. We have now performed a sequential study covering both early and late stages of the rejection response. We demonstrate that the early infiltrating killer cells are sensitive to anti-Ø and anti-T cell serum plus complement treatment but the late killer cells are not. This finding indicates that the first cytotoxic host cells infiltrating the allograft are predominantly T lymphocytes, whereas as the rejection process proceeds also cytotoxic non-T (“B”) lymphocytes and monocytes are recruited to the site of inflammation. 相似文献