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991.
Overexpression of the Matrix Metalloproteinase Matrilysin Results in Premature Mammary Gland Differentiation and Male Infertility 总被引:1,自引:0,他引:1 下载免费PDF全文
Laura A. Rudolph-Owen Paul Cannon Lynn M. Matrisian 《Molecular biology of the cell》1998,9(2):421-435
To examine the role of matrilysin (MAT), an epithelial cell-specific matrix metalloproteinase, in the normal development and function of reproductive tissues, we generated transgenic animals that overexpress MAT in several reproductive organs. Three distinct forms of human MAT (wild-type, active, and inactive) were placed under the control of the murine mammary tumor virus promoter/enhancer. Although wild-type, active, and inactive forms of the human MAT protein could be produced in an in vitro culture system, mutations of the MAT cDNA significantly decreased the efficiency with which the MAT protein was produced in vivo. Therefore, animals carrying the wild-type MAT transgene that expressed high levels of human MAT in vivo were further examined. Mammary glands from female transgenic animals were morphologically normal throughout mammary development, but displayed an increased ability to produce β-casein protein in virgin animals. In addition, beginning at approximately 8 mo of age, the testes of male transgenic animals became disorganized with apparent disintegration of interstitial tissue that normally surrounds the seminiferous tubules. The disruption of testis morphology was concurrent with the onset of infertility. These results suggest that overexpression of the matrix-degrading enzyme MAT alters the integrity of the extracellular matrix and thereby induces cellular differentiation and cellular destruction in a tissue-specific manner. 相似文献
992.
Alessandra de Cupis Paolo Pirani Laura Fazzuoli Roberto E. Favoni 《In vitro cellular & developmental biology. Animal》1998,34(10):836-843
Summary Growth rate, morphology, and responsiveness to mitogenic stimuli and pharmacological treatments were evaluated in early and
late cell passages derived from the same clone of the widely used MCF-7 human breast adenocarcinoma cell line. Our results
indicate dissimilarities between early (E) and late (L) passages for some of the parameters analyzed. The cells that underwent
many subcultivations grew faster than the others; both appeared homogeneous in size and shape. The E cells, subcultured for
almost 1 yr, displayed higher sensitivity to the mitogenic action of both estradiol, according to the level of estrogen receptor,
and insulin-like growth factor-I than did the L cells, kept in culture for more than 10 yr. Cell responsiveness to two drugs,
a novel steroid antiestrogen and a polysulfonated distamycin A derivative, was more pronounced in the early cultures only
at the longer time of exposure to the higher concentration of the estrogen antagonist. In addition, a drug-induced inhibition
of insulin-like growth factor-I binding to its receptor was shown in both E and L cells, the latter being less sensitive than
the former when exposed to the antiestrogen. Finally, MCF-7 E and L cells showed similar behavior when drug-induced apoptosis
was tested. 相似文献
993.
Nader Rahimi Eric Tremblay Laura McAdam Anita Roberts Bruce Elliott 《In vitro cellular & developmental biology. Animal》1998,34(5):412-420
Summary We have developed an in vitro system to examine the influence of adipocytes, a major mammary stromal cell type, on the growth of a murine mammary carcinoma,
SP1. Previously, we have shown that 3T3-L1 adipocytes release a mitogenic factor, hepatocyte growth factor, which strongly
stimulates proliferation of SP1 cells. We now show that 3T3-L1 pre-adipocytes secrete active inhibitory molecules which inhibit
DNA synthesis in SP1 cells. In addition, latent inhibitory activity is present in conditioned media (CM) from both pre-adipocytes
and adipocytes, and is activated following acid treatment. CM also inhibited DNA synthesis in Mv1Lu wild type epithelial cells,
but not DR27 mutant epithelial cells which lack TGF-β type II receptor. Inhibitory activity of CMs was partially abrogated
by neutralizing anti-TGF-β1 and anti-TGF-β2 antibodies, and was removed following ultrafiltration through membranes of 10
000 Mr but not 30 000 Mr pore size. These results show that the inhibitory effect on DNA synthesis is mediated by TGF-β1-like and TGF-β2-like molecules.
In addition, acid-treated CM as well as purified TGF-β inhibited differentiation of pre-adipocytes. Untreated pre-adipocyte
CM, but not mature adipocyte CM, spontaneously inhibited adipocyte differentiation. Together, these findings indicate that
pre-adipocytes spontaneously activate their own secreted TGF-β, whereas mature adipocytes do not, and suggest that activation
of TGF-β has a potent negative regulatory effect on adipocyte differentiation and tumor growth. Thus, TGF-β may be an important
modulator of tumor growth and adipocyte differentiation via both paracrine and autocrine mechanisms. These findings emphasize
the importance of adipocyte-tumor interactions in the regulation of tumor microenvironment. 相似文献
994.
Marina Gobbo Laura Biondi Fernando Filira Fernando Formaggio Marco Crisma Raniero Rocchi Claudio Toniolo Quirinus B. Broxterman Johan Kamphuis 《International journal of peptide research and therapeutics》1998,5(2-3):105-107
Summary A series of longer analogues of the C-peptide of RNAse A has been synthesized with the aim of assessing the helix induction
potential in water of α-methyl, α-amino acids at the N-terminus of the chain. The circular dichroism data indicate that one
isovaline residue is effective in increasing the helix content of the 13-residue peptide by about 7%. 相似文献
995.
This study examined the effects ofhyperhydration, exercise-induced dehydration, and oral fluidreplacement on physiological strain of horses during exercise-heatstress. On three occasions, six horses completed a 90-min exerciseprotocol (50% maximal O2 uptake,34.5°C, 48% relative humidity) divided into two 45-min periods(exercise I andexercise II) with a 15-min recoverybetween exercise bouts. In random order, horses receivedno fluid (NF), 10 liters of water (W), or a carbohydrate-electrolytesolution (CE) 2 h before exercise and between exercise bouts. Compared with NF, preexercise hyperhydration (W and CE) did not alter heart rate, cardiac output (), stroke volume (SV), corebody temperature, sweating rate (SR), or sweating sensitivity duringexercise I. In contrast, afterexercise II, exercise-induceddehydration in NF (decrease in body mass: NF, 5.6 ± 0.8%; W, 1.1 ± 0.4%; CE, 1.0 ± 0.2%) resulted in greater heat storage,with core body temperature ~1.0°C higher compared with W and CE.In exercise II, the greater thermalstrain in NF was associated with significant(P < 0.05) decreases in (10 ± 2%), SV (9 ± 3%), SR, and sweatingsensitivity. We concluded that 1)preexercise hyperhydration provided no thermoregulatory advantage;2) maintenance of euhydration byoral fluid replacement (~85% of sweat fluid loss) during exercise inthe heat was reflected in higher , SV, and SR withdecreased heat storage; and 3) W oran isotonic CE solution was equally effective in reducing physiological strain associated with exercise-induced dehydration and heat stress. 相似文献
996.
Laura Beizer 《Anthropology & education quarterly》1998,29(1):140-142
997.
Katrin Böhning-Gaese Laura I. González-Guzmán James H. Brown 《Evolutionary ecology》1998,12(7):767-783
One could predict that the capacity for travelling great distances might predispose long-distance migratory birds to be good colonists and to exhibit wider geographic distributions than their non-migratory or short-distance migratory relatives or non-volant mammals. This prediction is not supported by the data on avian biogeography. The distributions of species, genera and families of North American and Eurasian birds and mammals are indeed related to migratory status, but long-distance migratory birds exhibit a great deal of biogeographic regionalism. In particular, at all taxonomic levels their distributions tend to be confined to either the Eastern or Western Hemisphere, suggesting that there has been little successful east–west dispersal between North America and Eurasia. Compared to non-migratory birds, short-distance migratory birds and non-volant mammals, long-distance migrants appear to be subject to severe constraints on their physiology, behaviour and ecology, w hich have prevented colonization of distant regions. 相似文献
998.
Laura E. Brown Martin W. Nicholson Jessica E. Arama Audrey Mercer Alex M. Thomson Jasmina N. Jovanovic 《The Journal of biological chemistry》2016,291(27):13926-13942
The establishment of cell-cell contacts between presynaptic GABAergic neurons and their postsynaptic targets initiates the process of GABAergic synapse formation. GABAA receptors (GABAARs), the main postsynaptic receptors for GABA, have been recently demonstrated to act as synaptogenic proteins that can single-handedly induce the formation and functional maturation of inhibitory synapses. To establish how the subunit composition of GABAARs influences their ability to induce synaptogenesis, a co-culture model system incorporating GABAergic medium spiny neurons and the HEK293 cells, stably expressing different combinations of receptor subunits, was developed. Analyses of HEK293 cell innervation by medium spiny neuron axons using immunocytochemistry, activity-dependent labeling, and electrophysiology have indicated that the γ2 subunit is required for the formation of active synapses and that its effects are influenced by the type of α/β subunits incorporated into the functional receptor. To further characterize this process, the large N-terminal extracellular domains (ECDs) of α1, α2, β2, and γ2 subunits were purified using the baculovirus/Sf9 cell system. When these proteins were applied to the co-cultures of MSNs and α1/β2/γ2-expressing HEK293 cells, the α1, β2, or γ2 ECD each caused a significant reduction in contact formation, in contrast to the α2 ECD, which had no effect. Together, our experiments indicate that the structural role of GABAARs in synaptic contact formation is determined by their subunit composition, with the N-terminal ECDs of each of the subunits directly participating in interactions between the presynaptic and postsynaptic elements, suggesting the these interactions are multivalent and specific. 相似文献
999.
1000.
Canto-Canché B Guillén-Maldonado DK Peraza-Echeverría L Conde-Ferráez L James-Kay A 《Molecular biotechnology》2007,36(1):64-70
A bacterial artificial chromosome library of the causal agent of the Black Sigatoka leaf spot disease of banana and plantain,
Mycosphaerella fijiensis, has been constructed using a non-sphaeroplasting technique and characterized using both homologous and heterologous probes.
After first and a second size selection of PFGE-fractionated DNA, a ligation was obtained using a 1:4 molar ratio (insert:vector).
One hundred random clones were analyzed, and the mean insert size was estimated to be 90 kb. The range of the insert sizes
was between 40 and 160 kb. The highest percentage of inserts belonged to the range between 80 and 100 kb; 32% of the inserts
had 2 or 3 internal NotI sites. This library consists of 1920 clones, if the genomic size is at least 35 Mb, then this represents 4.9× genome equivalents,
which was supported by hybridization results with homologous and heterologous probes.
Blondy Canto-Canché and Diana Karina Guillén-Maldonado contributed equally to this work and should be regarded as co-first
authors. 相似文献